The empty boxes indicate that the patient has run out of his medication.
Chronic administration of high doses of glucocorticoids (GCs) (e.g., prednisone or prednisolone) and also other hormones such as oestrogens, progestins, androgens and growth hormone induce varying degrees of tolerance, resulting in a progressively decreased response to the effect of the drug, followed by dependence and rarely addiction.
The glucocorticoid withdrawal syndrome (GWS) has been considered a withdrawal reaction due to established physical dependence on supraphysiological GC levels.
The severity of GWS depends on the genetics and developmental history of the patient, on his environment, and on the phase and degree of dependence the patient has reached. Its management should include a temporary increase in the dose of GCs followed by gradual, slow tapering to a maintenance dose.

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

The most probable diagnosis is diabetic ketoacidosis. ABG is mandatory to look for acidosis and correct pH accordingly.

Hyperthyroid patients show significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and pa(O2) than healthy patients. This may of course lead to misdiagnosis of patients with hyperthyroidism as having hyperventilation syndrome.

The symptoms this female presented with in the OPD are major symptoms of hypothyroidism due to insufficient thyroid hormone.

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon. GLP-1 is released in response to meal intake.
The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the ileal brake mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake.
Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycaemia.

Classically, pheochromocytoma manifests with the following 4 characteristics:
– Headaches
– Palpitations
– Sweating
– Severe hypertension

The Endocrine Society, the American Association for Clinical Chemistry, and the European Society of Endocrinology have released clinical practice guidelines for the diagnosis and management of pheochromocytoma.
Biochemical testing via measurement of plasma free metanephrines or urinary fractionated metanephrines should be performed in patients suspected of having pheochromocytoma.

Catecholamines produced by pheochromocytomas are metabolized within chromaffin cells. Norepinephrine is metabolized to normetanephrine and epinephrine is metabolized to metanephrine. Because this process occurs within the tumour, independently of catecholamine release, pheochromocytomas are best diagnosed by measurement of these metabolites rather than by measurement of the parent catecholamines.

During pregnancy, profound changes in thyroid physiology occur to provide sufficient thyroid hormone (TH) to both the mother and foetus. This is particularly important during early pregnancy because the fetal thyroid starts to produce considerable amounts of TH only from approximately 20 weeks of gestation, until which time the foetus heavily depends on the maternal supply of TH. This supply of TH to the foetus, as well as increased concentrations of TH binding proteins (thyroxine-binding globulin) and degradation of TH by placental type 3 iodothyronine deiodinase, necessitate an increased production of maternal TH. This requires an intact thyroid gland and adequate availability of dietary iodine and is in part mediated by the pregnancy hormone human chorionic gonadotropin, which is a weak agonist of the thyroid-stimulating hormone (TSH) receptor. As a consequence, serum-free thyroxine (FT4) concentrations increase and TSH concentrations decrease from approximately the eighth week throughout the first half of pregnancy, resulting in different reference intervals for TSH and FT4 compared to the non-pregnant state.

A fasting blood glucose level from 110 to 126 mg/dL (5.5 to 6.9 mmol/L) is considered prediabetes. This result is sometimes called impaired fasting glucose.
Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by plasma glucose. If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

Premature ovarian failure presents before the age of 40 in females with a triad of symptoms: amenorrhea, hypergonadism and low oestradiol. This triad is present in the patient.

This patient has hypercalcaemia due to hyperparathyroidism. However, the intestinal absorption of calcium is mainly controlled by 1,25 dihydroxy-vitamin D. Under the influence of calcitriol (active form of vitamin D), intestinal epithelial cells increase their synthesis of calbindin (calcium-binding carrier protein) necessary for active calcium ion absorption.

The level of haemoglobin A1c (HbA1c), also known as glycated haemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8-12 weeks. Recent studies have been made to correlate between HbA1c and average glucose level.
Using the following formula: Average blood glucose (mmol/l) = (1.98 x 1 HbA1c) – 4.29

The presence of the pulses excluded Thromboangitis Obliterans. The pain is not suggestive of sciatica. The history doesn’t support a DVT or an embolus as there is no pain at rest, swelling or skin changes. So the most probable diagnosis is atherosclerosis as the chronic diabetes and smoking support it.

Pregnancies affected by T1DM are at increased risk for preterm delivery, preeclampsia, macrosomia, shoulder dystocia, intrauterine fetal demise, fetal growth restriction, cardiac and renal malformations, in addition to rare neural conditions such as sacral agenesis.
Successful management of pregnancy in a T1DM patient begins before conception. Research indicates that the implementation of preconception counselling, emphasizing strict glycaemic control before and throughout pregnancy, reduces the rate of perinatal mortality and malformations.
The 2008 bulletin from the National Institute for Health and Clinical Excellence recommends that preconception counselling be offered to all patients with diabetes. Physicians are advised to guide patients on achieving personalized glycaemic control goals, increasing the frequency of glucose monitoring, reducing their HbA1C levels, and recommend avoiding pregnancy if the said level is > 10%.
Other sources suggest deferring pregnancy until HbA1C levels are > 8%, as this margin is associated with better outcomes.

A diabetic patient is a patient with depressed immunity. It is not uncommon to develop abscesses. Diabetic patients have a defected cellular innate immunity. On the other hand, bacteria become much more virulent in a high glucose environment in the interstitium.

Impaired glucose tolerance is a pre-diabetic state of hyperglycaemia that is associated with insulin resistance and increased risk of cardiovascular pathology. To diagnose impaired glucose tolerance, the OGTT value after 2 hrs should be 140-199mg/dl (7.7 – 11.0 mmol/l). Impaired fasting glucose is diagnosed as fasting blood sugar between 100 mg/dl to 125 mg/dl.

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.
Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess.
Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.
Normal Ultrasound rules out Turner’s syndrome.

Thiamine deficiency is very common with alcoholism. It manifests by Wernicke-Korsakoff encephalopathy. The patient is usually agitated, with an abnormal gait and amnesia.

Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis.
Patients with thyroid storm should be treated in an ICU setting for close monitoring of vital signs and for access to invasive monitoring and inotropic support, if necessary.
– Supportive measures
If needed, immediately provide supplemental oxygen, ventilatory support, and intravenous fluids. Dextrose solutions are the preferred intravenous fluids to cope with continuously high metabolic demand.
– Correct electrolyte abnormalities.
– Treat cardiac arrhythmia, if necessary.
– Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering acetaminophen (15 mg/kg orally or rectally every 4 hours).
– Antiadrenergic drugs.
– Thionamides: Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis of thyroid hormones (THs).
High-dose propylthiouracil (PTU) or methimazole may be used for treatment of thyroid storm.
– Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism and improving vasomotor symptoms.
– Bile acid sequestrants prevent reabsorption of free THs in the gut (released from conjugated TH metabolites secreted into bile through the enterohepatic circulation).
– Treat the underlying condition.

Lactic acidosis is occasionally responsible for metabolic acidosis in diabetics. It may occur in the presence of normal blood levels of the ketone bodies, and such cases are often described as having non-ketotic diabetic acidosis.
It is most commonly associated with tissue hypoperfusion and states of acute circulatory failure.
Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source, early antimicrobial intervention, and resection of any potential ischemic regions. Reassessment of lactate levels for clearance assists ongoing medical management.

It has been determined that HPV infection is the most powerful epidemic factor. This virus is needed, but not sufficient for the development of cervical cancer.
The WHO’s International Agency for Research on Cancer (IARC) classified HPV infection as carcinogenic to humans (HPV types 16 and 18), probably carcinogenic (HPV types 31 and 33) and possibly carcinogenic (other HPV types except 6 and 11).
Tobacco smoking, the use of contraceptives, and the number of births are factors that showed no statistically significant deviations in the studied population compared to other countries in the region, as well as European countries. They have an equal statistical significance in all age groups.

The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

Euthyroid sick syndrome (also known as nonthyroidal illness syndrome) can be described as abnormal findings on thyroid function tests that occurs in the setting of a nonthyroidal illness (NTI), without pre-existing hypothalamic-pituitary and thyroid gland dysfunction. After recovery from an NTI, these thyroid function test result abnormalities should be completely reversible.
Multiple alterations in serum thyroid function test findings have been recognized in patients with a wide variety of NTIs without evidence of pre-existing thyroid or hypothalamic-pituitary disease. The most prominent alterations are low serum triiodothyronine (T3) and elevated reverse T3 (rT3), leading to the general term low T3 syndrome. Thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 (FT4), and free T4 index (FTI) also are affected in variable degrees based on the severity and duration of the NTI. As the severity of the NTI increases, both serum T3 and T4 levels drop, but they gradually normalize as the patient recovers.
Reverse T3 is used to differentiate between this condition and secondary thyroid failure.

Hypercalcemia is the most important finding in all types of malignancies. In myeloma it is especially caused by osteoclast activating factors which increase bone turnover.

Achondroplasia is the most common type of short-limb disproportionate dwarfism. A single gene mapped to the short arm of chromosome 4 (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait. All people with achondroplasia have a short stature.
Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Examination of the infant after birth shows increased front-to-back head size. There may be signs of hydrocephalus. It may be diagnosed radiographically at birth, or becomes obvious within the first year with disparity between a large skull, normal trunk length and short limbs.

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Approximately 95% of patients with type 1 DM have either HLA-DR3 or HLA-DR4. Although the genetic aspect of type 1 DM is complex, with multiple genes involved, there is a high sibling relative risk. Whereas dizygotic twins have a 5-6% concordance rate for type 1 DM, monozygotic twins will share this diagnosis more than 50% of the time by the age of 40 years.

Increased levels of prolactin in men can lead to erectile dysfunction, reduced facial and body hair and on rare occasion gynecomastia with galactorrhoea.

According to the criteria of the World Health Organization and the American Diabetes Association, impaired glucose tolerance is defined as:
two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol/l) on the 75-g oral glucose tolerance test.

Treated breast malignancy is pointing towards hypercalcemia as it is very common in patients of CA. The symptoms of hypercalcemia are increased thirst, drowsiness and confusion.

In SIADH, there is increased secretion of the ADH hormone resulting in increased water absorption. That’s why there would be decreased serum Na, decreased osmolarity and increased urine osmolarity.

A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. There are six antimuscarinic drugs currently marketed for the treatment of urge incontinence: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin.

Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus.

Some patients return spontaneously to a euthyroid state within a few months, but most patients experience a phase of hypothyroidism that takes 2 to 6 months to resolve; of this group, some develop permanent hypothyroidism. About 50% of patients, however, will develop permanent hypothyroidism within 5 years of the diagnosis of postpartum thyroiditis.

High titres of anti-TPO antibodies during pregnancy have been reported to have high sensitivity and specificity for postpartum autoimmune thyroid disease.

Only immunoglobulins are required, as he is already immunized.

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

Criteria for the diagnosis of diabetes

1. A1C >6.5%. The test should be performed in a laboratory using a method that is certified and standardized.*
OR
2. Fasting glucose >126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*
OR
3. 2-h plasma glucose >200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycaemia or hyperglycaemic crisis, a random plasma glucose >200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycaemia, criteria 1-3 should be confirmed by repeat testing.

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.
Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:
Short stature
Stocky habitus
Obesity
Developmental delay
Round face
Dental hypoplasia
Brachymetacarpals
Brachymetatarsals
Soft tissue calcification/ossification
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.
The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

The patient is most likely to have Addison’s disease as he has a history of autoimmune disease, hyperkalaemia and hypotension.
It is important to keep an Addisonian crisis on the differential in cases of shock, especially since adrenal crisis can be the patient’s first presentation of adrenal insufficiency.
Patients with Addison’s disease are prone to developing hypoglycaemia due to loss of the glucogenic effect of glucocorticoids. Given the sudden deterioration, a glucose level must be checked.

For medical management of carcinoid syndrome, there are two somatostatin analogues available, Octreotide and Lanreotide. Somatostatin is an amino acid peptide which is an inhibitory hormone, which is synthesized by paracrine cells located ubiquitously throughout the gastrointestinal tract. Both somatostatin analogues provide symptom relief in 50% to 70% of patients and biochemical response in 40% to 60% patients. Many studies have shown that Octreotide and Lanreotide also inhibit the proliferation of tumour cells.

All the symptoms this patient is suffering from are the classic features of a hypothyroid state.

Patients with diabetes often develop ophthalmic complications, the most common and potentially most blinding of these complications is diabetic retinopathy.
The following are the 5 stages in the progression of diabetic retinopathy:
1. Dilation of the retinal venules and formation of retinal capillary microaneurysms.
2. Increased vascular permeability.
3. Vascular occlusion and retinal ischemia.
4. Proliferation of new blood vessels on the surface of the retina.
5. Vitreous haemorrhage and contraction of the fibrovascular proliferation.
The first 2 stages of diabetic retinopathy are known as background or nonproliferative retinopathy. Initially, the retinal venules dilate, then microaneurysms (tiny red dots on the retina that cause no visual impairment) appear. As the microaneurysms or retinal capillaries become more permeable, hard exudates appear, reflecting the leakage of plasma.

Mild nonproliferative diabetic retinopathy (NPDR) or background diabetic retinopathy is indicated by the presence of at least 1 microaneurysm, while neovascularization is the hallmark of Proliferative Diabetic Retinopathy (PDR).

The key features of MODY are: being diagnosed with DM under the age of 15, having a parent with DM, and DM in two or more generations of the family.

RET (rearranged during transfection) is a receptor tyrosine kinase involved in the development of neural crest derived cell lineages, kidney, and male germ cells. Different human cancers, including papillary and medullary thyroid carcinomas, lung adenocarcinomas, and myeloproliferative disorders display gain-of-function mutations in RET.
In over 90% of cases, MEN2 syndromes are due to germline missense mutations of the RET gene.
Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumours, and pheochromocytoma.

She has steroid induced hyperglycaemia. She needs satisfactory glycaemic control to avoid post surgical infections. As she is in a stressful event following a major surgery, insulin is the best method to manage her hyperglycaemia.

Carcinoid tumours are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. They can be seen in other organs, including the lungs, mediastinum, thymus, liver, bile ducts, pancreas, bronchus, ovaries, prostate, and kidneys. While carcinoid tumours tend to grow slowly, they have the potential to metastasise.
Signs and symptoms seen in larger tumours may include the following:
– Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome.
– Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck.
– Diarrhoea and malabsorption (84%): Watery, frothy, or bulky stools, gastrointestinal (GI) bleed or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps.
– Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure with tachycardia and hypertension.
– Wheezing or asthma-like syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnoea.
– Pellagra with scale-like skin lesions, diarrhoea and mental disturbances.
– Carcinoid crisis can be the most serious symptom of the carcinoid tumours and life-threatening. It can occur suddenly or after stress, including chemotherapy and anaesthesia.

Acromegaly occurs due to excessive action of insulin-like growth factor I (IGF-I) after the growth plate cartilage fuses in adulthood.
It can be an insidious disease. Symptoms, which may precede diagnosis by several years, can be divided into the following groups:
1. Symptoms due to local mass effects of an intracranial tumour
Tumour damage to the pituitary stalk may cause hyperprolactinemia (Increased blood prolactin levels associated with galactorrhoea) due to loss of inhibitory regulation of prolactin secretion by the hypothalamus
2. Symptoms due to excess of GH/IGF-I including:
– Hyperhidrosis (Not hypohidrosis)
– Arthritis
– Peripheral Neuropathies e.g. Carpal Tunnel Syndrome

Biguanides (Metformin):
People who take metformin alone should be able to fast safely given that the possibility of hypoglycaemia is minimal. However, patients should modify its dose and administration timing to provide two-thirds of the total daily dose, which should be taken immediately with the sunset meal, while the other third is taken before the predawn meal.

Thiazolidinediones: No change needed.

Sulfonylurea:
Once-daily sulfonylurea (such as glimepiride or gliclazide MR): the total daily dose should be taken with the sunset meal.
Shorter-acting sulfonylurea (such as gliclazide twice daily): the same daily dose remains unchanged, and one dose should be taken at the sunset meal and the other at the predawn meal.
Long-acting sulfonylurea (such as glibenclamide): these agents should be avoided.

It is important that diabetic patients to eat a healthy balanced diet and choose foods with a low glycaemic index (such as complex carbohydrates), which can help to maintain blood glucose levels during fasting. Moreover, it is crucial to consume adequate fluids to prevent dehydration. Physical activity is encouraged, especially during non-fasting periods.

Primary hyperparathyroidism (PHPT) is diagnosed based upon levels of blood calcium and parathyroid hormone (PTH). In most people with PHPT, both levels are higher than normal. Occasionally, a person may have an elevated calcium level and a normal or minimally elevated PTH level. Since PTH should normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates PHPT.

These symptoms represent hemiballismus which is common in diabetic patients after the infarction of contralateral subthalmic nucleus. These symptoms are usually present during activity phase and resolve while resting.

11-beta hydroxylase is stimulated by ACTH and responsible for conversion of 11-deoxycortisol to cortisol and deoxycorticosterone to corticosterone.

In 11-beta hydroxylase deficiency, the previously mentioned conversions are partially blocked, leading to:
– Increased levels of ACTH
– Accumulation of 11-deoxycortisol (which has limited biological activity) and deoxycorticosterone (which has mineralocorticoid activity)
– Overproduction of adrenal androgens (DHEA, androstenedione, and testosterone)

Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 is considered mild or subclinical hypothyroidism.
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be asymptomatic. Symptoms and signs are often subtle and neither sensitive nor specific.
The following are symptoms of hypothyroidism:
– Fatigue, loss of energy, lethargy
– Weight gain
– Decreased appetite
– Cold intolerance
– Dry skin
– Hair loss
– Sleepiness
– Muscle pain, joint pain, weakness in the extremities
– Depression
– Emotional lability, mental impairment
– Forgetfulness, impaired memory, inability to concentrate
– Constipation
– Menstrual disturbances, impaired fertility
– Decreased perspiration
– Paraesthesia and nerve entrapment syndromes
– Blurred vision
– Decreased hearing
– Fullness in the throat, hoarseness
Physical signs of hypothyroidism include the following:
– Weight gain
– Slowed speech and movements
– Dry skin
– Jaundice
– Pallor
– Coarse, brittle, straw-like hair
– Loss of scalp hair, axillary hair, pubic hair, or a combination
– Dull facial expression
– Coarse facial features
– Periorbital puffiness
– Macroglossia
– Goitre (simple or nodular)
– Hoarseness
– Decreased systolic blood pressure and increased diastolic blood pressure
– Bradycardia
– Pericardial effusion
– Abdominal distention, ascites (uncommon)
– Hypothermia (only in severe hypothyroid states)
– Nonpitting oedema (myxoedema)
– Pitting oedema of lower extremities
– Hyporeflexia with delayed relaxation, ataxia, or both.

Conn’s disease is a condition in which excessive amounts of aldosterone are secreted from the adrenal glands. Because aldosterone increases the reabsorption of sodium, it leads to a very high blood pressure.

Patients who have autonomously functioning nodules should be treated definitely with radioactive iodine or surgery.
Na131 I treatment – In the United States and Europe, radioactive iodine is considered the treatment of choice for Toxic Nodular Goitre. Except for pregnancy, there are no absolute contraindications to radioiodine therapy.

The patient has primary Hypogonadism.
Since he already had two children, Klinefelter syndrome is excluded and the patient does not need karyotyping.
His lab results are normal indicating normal pituitary gland functions.
So the next step is testicular ultrasound as testicular tumour, infiltration or idiopathic failure is suspected.

This scenario represents anorexia nervosa disorder, a psychological disorder. Extreme weight loss with a strict diet can lead to deficiency of many nutrients like magnesium and calcium. This can also cause amenorrhea.

The frequency of type-1 diabetes is higher in siblings of diabetic parents (e.g., in the UK 6% by age 30) than in the general population (in the U.K. 0.4% by age 30), while disease concordance in monozygotic (identical) twins is about 40% i.e. the risk that the unaffected twin will develop diabetes.

The patient has hyperprolactinaemia with otherwise normal oestradiol, FSH and LH. This is highly suggestive of Prolactinoma rather than a non functioning tumour.
In polycystic ovaries, there is increase in the level of LH while FSH is normal or low.

Surgical incision and drainage is the most common treatment for anal abscesses. About 50% of patients with an anal abscess will develop a complication called a fistula. Diabetes is a risk factor for an anal abscess.

Propylthiouracil (PTU) is a safe choice for a woman that is planning a pregnancy because it does not have the teratogenic effects as carbimazole does. Methimazole (MMI) and propylthiouracil (PTU) are the standard anti-thyroid drugs used in the treatment of hyperthyroidism in pregnancy. Carbimazole can cause spina bifida, CV malformations as well as hypospadia.

The water deprivation test (i.e., the Miller-Moses test), is a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis. It is typically performed in patients with more chronic forms of Diabetes Insipidus (DI). The extent of deprivation is usually limited by the patient’s thirst or by any significant drop in blood pressure or related clinical manifestation of dehydration.

In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma osmolality. Additionally, in normal, healthy subjects, administration of ADH produces an increase of less than 9% in urinary osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.

In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality will be above 750 mOsm/kg after water deprivation.
A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia.

European guidelines for the treatment of syndrome of inappropriate antidiuresis include the following recommendations for the management of moderate or profound hyponatremia:
– Restrict fluid intake as first-line treatment.
– Second-line treatments include increasing solute intake with 0.25-0.50 g/kg per day or a combination of low-dose loop diuretics and oral sodium chloride.
– Use of lithium, demeclocycline, or vasopressin receptor antagonists is not recommended.
Recommendations on the treatment of SIADH from an American Expert Panel included the following:
– If chronic, limit the rate of correction.
– Fluid restriction should generally be first-line therapy.
– Consider pharmacologic therapies if serum Na + is not corrected after 24-48 hr of fluid restriction or if the patient has a low urinary electrolyte free water excretion.
– Patients being treated with vaptans should not be on a fluid restriction initially.
– Water, 5% dextrose or desmopressin can be used to slow the rate of correction if the water diuresis is profound.

The patient has hyperinsulinemia and hypoglycaemia, but her C-peptide levels are normal. This is strongly suggestive of the fact that she is self-administering insulin.
In Insulinoma, common diagnostic criteria include:
– blood glucose level < 50 mg/dl with hypoglycaemic symptoms,
– relief of symptoms after eating
– absence of sulfonylurea on plasma assays.
The classic diagnostic criteria include the demonstration of the following during a supervised fast:
Increased plasma insulin level
Increased C peptide level
Increased proinsulin level
However, the patient has normal C-peptide levels.
In type-1 diabetes mellitus, insulin and C-peptide levels are low.

Primary aldosteronism now is considered one of the more common causes of secondary hypertension (HTN).
Individuals with primary aldosteronism may present with hypokalaemia metabolic alkalosis; however, as many as 38% of patients with primary aldosteronism may be normokalaemia at presentation.
Routine laboratory studies can show hypernatremia, hypokalaemia, and metabolic alkalosis resulting from the action of aldosterone on the renal distal convoluted tubule (DCT) (i.e., enhancing sodium reabsorption and potassium and hydrogen ion excretion).
Plasma aldosterone/plasma renin activity ratio is used for screening because it is fairly constant over many physiologic conditions.

The patient is clinically free, so Cushing diseases can be exclude.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

In patients with polycystic ovarian syndrome (PCOS), FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated for Tanner stage, sex, and age. The LH-to-FSH ratio is usually greater than 3.

Women with PCOS have abnormalities in the metabolism of androgens and oestrogen and in the control of androgen production. PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis.
The major features of PCOS include menstrual dysfunction, anovulation, and signs of hyperandrogenism. Other signs and symptoms of PCOS may include the following:
– Hirsutism
– Infertility
– Obesity and metabolic syndrome
– Diabetes
– Obstructive sleep apnoea

Androgen excess can be tested by measuring total and free testosterone levels or a free androgen index. An elevated free testosterone level is a sensitive indicator of androgen excess. Other androgens, such as dehydroepiandrosterone sulphate (DHEA-S), may be normal or slightly above the normal range in patients with polycystic ovarian syndrome (PCOS). Levels of sex hormone-binding globulin (SHBG) are usually low in patients with PCOS.

Some women with PCOS have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one-third of women with PCOS who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by 30 years of age.

Osteopenia is an early sign of bone weakening that is less severe than osteoporosis.
The numerical result of the bone density test is quantified as a T score. The lower the T score, the lower the bone density. T scores greater than -1.0 are considered normal and indicate healthy bone. T scores between -1.0 and -2.5 indicate osteopenia. T scores lower than -2.5 indicate osteoporosis.
DEXA also provides the patient’s Z-score, which reflects a value compared with that of person matched for age and sex.
Z-score values of -2.0 SD or lower are defined as below the expected range for age and those above -2.0 SD as within the expected range for age.

Several dipeptidyl peptidase-4 (DPP-4) inhibitors are in clinical development; these are orally active and increase levels of active glucagon-like peptide-1 (GLP-1), which in turn increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels.
Sitagliptin and vildagliptin both have a long duration of action, allowing once-daily administration. Both sitagliptin and vildagliptin are safe and tolerable with a low risk of hypoglycaemia. In drug-naïve subjects with type 2 diabetes, both sitagliptin and vildagliptin reduce A1C levels by ,1% as monotherapy.

Bicarbonate therapy is not indicated in mild and moderate forms of DKA because metabolic acidosis will correct with insulin therapy. The use of bicarbonate in severe DKA is controversial due to a lack of prospective randomized studies. It is thought that the administration of bicarbonate may actually result in peripheral hypoxemia, worsening of hypokalaemia, paradoxical central nervous system acidosis, cerebral oedema in children and young adults, and an increase in intracellular acidosis. Because severe acidosis is associated with worse clinical outcomes and can lead to impairment in sensorium and deterioration of myocardial contractility, bicarbonate therapy may be indicated if the pH is 6.9 or less.

The history is suggestive of gastric carcinoma with dysphagia, vomiting, weight loss and lymphatic metastasis to the supraclavicular node, known as Virchow’s node.

Hyperthyroidism is characterised by heat intolerance, loss of weight, increased sweating, increased bowel frequency and tachycardia. On GPE, there might be proptosis of eyes and tremors in the hands.

Impaired glucose tolerance means that blood glucose is raised beyond normal levels, but not high enough to warrant a diabetes diagnosis. With impaired glucose tolerance you face a much greater risk of developing diabetes and cardiovascular disease. Impaired glucose tolerance is defined as 2-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in fasting patients.

Patients suffering from Addison’s disease have low aldosterone. Aldosterone increases Na+ absorption and excretion of K+. So in these patients there would be decreased Na+ and increased K+ levels.

A low haemoglobin and a high retic count is suggestive of a haemolytic anaemia. Occasional spherocytes can be seen on blood film during haemolysis and it is not a specific finding. Direct Coombs test will help to identify autoimmune haemolytic anaemia, where there are antibodies attached to RBCs.

Weight loss is most commonly linked to hyperthyroidism. An overactive thyroid gland (hyperthyroidism) or underactive thyroid gland (hypothyroidism) can cause menstrual irregularities, including amenorrhea. In this scenario, we would carry out thyroid function tests.

Exposure to excessive androgens is usually accompanied by premature epiphyseal maturation and closure, resulting in a final adult height that is typically significantly below that expected from parental heights.

congenital adrenal hyperplasia (CAH) is associated with precocious puberty caused by long term exposure to androgens, which activate the hypothalamic-pituitary-gonadal axis. Similarly, CAH is associated with hyperpigmentation and hyperreninemia due to sodium loss and hypovolaemia.

These symptoms are suggestive of thyrotoxicosis. In this disease, the basal metabolic rate of the patients is increased due to excessive thyroid hormones in the blood.

Dapagliflozin works by inhibiting sodium glucose cotransporter 2 (SGLT2) and blocking resorption of glucose in the kidney, leading to an increase in urinary glucose excretion and lowering of both plasma glucose levels and body weight.
All studies with SGLT2 inhibitors have found significant reductions in BP, with greater reductions seen in systolic (1.66 to 6.9mmHg) than diastolic (0.88 to 3.5mmHg) BP.
While some trials have shown no change in lipid parameters, others have shown a modest but statistically significant increase in both HDL and LDL cholesterol with no effect on triglycerides or the LDL/HDL ratio.

Insulin remains the standard of care for the treatment of uncontrolled gestational diabetes. Tight control maintained in the first trimester and throughout pregnancy plays a vital role in decreasing poor fetal outcomes, including structural anomalies, macrosomia, hypoglycaemia of the new-born, adolescent and adult obesity, and diabetes.
The baby is already large for dates so nutritional therapy can not be used alone.

The patient is most likely to have Postpartum thyroiditis which goes through 2 phases; hypothyroid and a hyperthyroid phase.
The hyperthyroid phase of postpartum thyroiditis occurs between 2 and 10 months postpartum. Most commonly, it presents at 3 months. Symptoms more common in women with hyperthyroid postpartum thyroiditis include palpitations, fatigue, heat intolerance, and irritability/nervousness. The frequency of asymptomatic hyperthyroidism is 33%.
Untreated, the hyperthyroidism resolves spontaneously within 2-3 months. This phase is diagnosed by the combination of a low serum TSH concentration in the presence of thyroid peroxidase antibodies, in women who are TSH receptor antibody-negative. Free T4 levels are typically elevated but may be normal.
Treatment of hyperthyroidism, when necessary, is based on symptom severity and should be a joint decision of patient and physician. Beta-blockers such as propranolol are given to alleviate palpitations, irritability, and nervousness. The morbidity associated with treatment is the side effects of beta-blockade. The downside of withholding treatment is allowing the woman to remain symptomatic. Antithyroid medicines (thioureas) are not a potential treatment alternative, because the hyperthyroidism is caused by destructive thyroiditis resulting in the release of preformed thyroid hormone.

The patient has Cushing syndrome suggested by the elevated 24hr urine free cortisol. Hence, the mass is most probably a cortisol secreting adenoma.

The boy has an increased BMI which implies he is overweight. Possible trauma to his pancreas might have led to a diabetes-like condition, induced by damage to the beta cells. Fasting blood glucose should be measured as a follow-up strategy to see if the damage is reversible or irreversible and to conclude if the glycosuria is related to his metabolic profile or to his accident.

Cabergoline, an ergot derivative, is a long-acting dopamine agonist. It is usually better tolerated than Bromocriptine (BEC), and its efficacy profiles are somewhat superior to those of BEC. It offers the convenience of twice-a-week administration, with a usual starting dose of 0.25 mg biweekly to a maximum dose of 1 mg biweekly. Some studies have shown efficacy even with once-a-week dosing. Cabergoline appears to be more effective in lowering prolactin levels and restoring ovulation. Up to 70% of patients who do not respond to BEC respond to cabergoline.

The patient most likely has Klinefelter’s syndrome.
Klinefelter syndrome (KS) refers to a group of chromosomal disorders in which the normal male karyotype, 46,XY, has at least one extra X chromosome. XXY aneuploidy, the most common human sex chromosome disorder. It is also the most common chromosomal disorder associated with male hypogonadism and infertility.
Klinefelter syndrome is characterized by hypogonadism (micro-orchidism, oligospermia/azoospermia), gynecomastia in late puberty, hyalinization and fibrosis of the seminiferous tubules, elevated urinary gonadotropin levels, and behavioural concerns.

Synacthen test interpretation:
– Basal Cortisol level should be greater than 180nmol/L
– 30min or 60min Cortisol should be greater than 420nmol/L (whatever the basal level)
– The increment should be at least 170nmol/L, apart from in severely ill patients where adrenal output is already maximal.
The patient’s results show that she has Acute Adrenal Insufficiency
The guidelines include the following recommendations for emergency treatment:
Administer hydrocortisone: Immediate bolus injection of 100 mg hydrocortisone intravenously or intramuscularly followed by continuous intravenous infusion of 200 mg hydrocortisone per 24 hours (alternatively, 50 mg hydrocortisone per intravenous or intramuscular injection every 6 h)
Rehydrate with rapid intravenous infusion of 1000 mL of isotonic saline infusion within the first hour, followed by further intravenous rehydration as required (usually 4-6 L in 24 h; monitor for fluid overload in case of renal impairment and elderly patients)
Contact an endocrinologist for urgent review of the patient, advice on further tapering of hydrocortisone, and investigation of the underlying cause of the disease, including the diagnosis of primary versus secondary adrenal insufficiency
Tapering of hydrocortisone can be started after clinical recovery guided by an endocrinologist; in patients with primary adrenal insufficiency, mineralocorticoid replacement must be initiated (starting dose 100 μg fludrocortisone once daily) as soon as the daily glucocorticoid dose is below 50 mg of hydrocortisone every 24 hours

Severe vitamin C deficiency results in scurvy, a disorder characterized by hemorrhagic manifestations and abnormal osteoid and dentin formation.
Vitamin C plays a role in collagen, carnitine, hormone, and amino acid formation. It is essential for bone and blood vessel health and wound healing and facilitates recovery from burns. Vitamin C is also an antioxidant, supports immune function, and facilitates the absorption of iron (see table Sources, Functions, and Effects of Vitamins).
Dietary sources of vitamin C include citrus fruits, tomatoes, potatoes, broccoli, strawberries, and sweet peppers. (See also Overview of Vitamins.)

Klinefelter syndrome (KS), the most common human sex chromosome disorder 47,XXY. It is characterized by hypogonadism (micro-orchidism, oligospermia/azoospermia) and gynecomastia in late puberty. If Klinefelter syndrome is not diagnosed prenatally, a patient with 47,XXY karyotype may demonstrate various subtle, age-related clinical signs that would prompt diagnostic testing. These include the following:
Infants: Hypospadias, small phallus, cryptorchidism.
Toddlers: Developmental delay (especially expressive language skills), hypotonia.
Older boys and adolescent males: Tall stature; delayed or incomplete pubertal development with eunuchoid body habitus; gynecomastia; small, firm testes; sparse body hair.

From childhood with progression to early puberty, the pituitary-gonadal function observed is within normal limits for 47,XXY males.
At mid puberty and later, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations rise to hyper-gonadotropic levels, inhibin B levels fall until they are undetectable, and testosterone levels are at low or low-normal levels after an initial increase.

Fragile X syndrome, also termed Martin-Bell syndrome or marker X syndrome, is the most common cause of inherited mental retardation, intellectual disability, and autism.
However, the patient here does not have any mental disabilities as he already works as a clerk, and that too would make Down’s Syndrome less likely.

Classic Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) are rare genetic conditions that encompass the spectrum of isolated hypogonadotropic hypogonadism. Most patients have gonadotropin-releasing hormone (GnRH) deficiency, as suggested by their response to pulsatile GnRH therapy. Hypothalamic-pituitary function is otherwise normal in most patients, and hypothalamic-pituitary imaging reveals no space-occupying lesions. By definition, either anosmia or severe hyposmia is present in patients with Kallmann syndrome, in contrast to patients with idiopathic hypogonadotropic hypogonadism, whose sense of smell is normal.

Transient congenital hypothyroidism can be due to: iodine deficiency or excess, maternal consumption of goitrogens or antithyroid medications during pregnancy, transplacental passage of TSH receptor-blocking antibodies, and neonatal very low birth weight and prematurity

The clinical manifestations of Small cell lung cancer (SCLC) can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome that is frequently associated with lung cancer; however, the incidence of clinically apparent HPO is not well known.
SIADH is present in 15% of cases and most commonly seen.
Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases.
Ectopic Cushing’s syndrome in SCLC does not usually exhibit the classic signs of Cushing’s syndrome and Cushing’s syndrome could also appear during effective chemotherapy.
Chemotherapy is the treatment of choice in SCLC.

Raloxifene is a selective oestrogen-receptor modulator (SERM) that has been approved for use in the prevention and treatment of osteoporosis in postmenopausal women.
A SERM interacts with oestrogen receptors, functioning as an agonist in some tissues and an antagonist in other tissues. Because of their unique pharmacologic properties, these agents can achieve the desired effects of oestrogen without the possible stimulatory effects on the breasts or uterus.

Three classes of medications are appropriate for the management of major triglyceride elevations: fibric acid derivatives, niacin, and omega-3 fatty acids.

Fibrate is used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

High-dose niacin (vitamin B-3) (1500 or more mg/d) decreases triglyceride levels by at least 40% and can raise HDL cholesterol levels by 40% or more. Niacin also reliably and significantly lowers LDL cholesterol levels, which the other major triglyceride-lowering medications do not.

Omega-3 fatty acids are attractive because of their low risk of major adverse effects or interaction with other medications. At high doses (>4 g/d), triglycerides are reduced.

The patient’s age and symptoms suggest Grave’s disease with thyroid-associated ophthalmopathy. In Grave’s disease, weight loss is noticed regardless of normal eating habits of the patient. Palpitations are also typical and may be confused with a panic attack. Proptosis is usually bilateral, but unilateral is also possible.

Insulin is produced by the beta-cells in the islets of Langerhans in the pancreas while Glucagon is secreted from the alpha cells of the pancreatic islets of Langerhans.
Type 1 diabetes mellitus is the culmination of lymphocytic infiltration and destruction of the beta cells of the islets of Langerhans in the pancreas. As beta-cell mass declines, insulin secretion decreases until the available insulin is no longer adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycaemia develops and diabetes may be diagnosed.

This patient is most likely suffering from diabetes mellitus. Diagnosis of DM involves checking for elevated blood glucose levels (hyperglycaemia).

Prolactinomas, benign lesions that produce the hormone prolactin, are the most common hormone-secreting pituitary tumours.
Based on its size, a prolactinoma can be classified as a microprolactinoma (< 10 mm diameter) or a macroprolactinoma (>10 mm diameter). If the prolactinoma is large enough to compress the surrounding normal hormone-secreting pituitary cells, it may result in deficiencies of one or more hormones (e.g., thyroid-stimulating hormone [TSH], growth hormone [GH], adrenocorticotropic hormone). However, the patient has microadenoma so it is unlikely to cause compression manifestations.
Hyperprolactinemia inhibits GnRH secretion from the medial basal hypothalamus and LH release from the pituitary.

Paget’s disease of bone is a chronic disease of the skeleton. In healthy bone, a process called remodeling removes old pieces of bone and replaces them with new, fresh bone. Paget’s disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Paget’s disease most often affects older people, occurring in approximately 2 to 3% of the population over the age of 55.

Many patients with Paget’s disease have no symptoms at all and are unaware they have the disease until X-rays are taken for some other reason. When bone pain and other symptoms are present, they can be related to the disease itself or to complications that arise from the disease — such as arthritis, bone deformity, and fractures. In patients with Paget’s disease, alkaline phosphatase levels are usually quite elevated — a reflection of the high bone turnover rate.

The presentation is highly suggestive of a hypoglycaemic episode, which is more common amongst older patient with diabetes mellitus. The chance of hypoglycaemia is higher with insulin users. Blood sugar measurement is crucial in the management.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
– Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
– Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney
This patient has the central type from metastases.
In patients with central DI, desmopressin is the drug of choice. It is a synthetic analogue of antidiuretic hormone (ADH). It is available in subcutaneous, IV, intranasal, and oral preparations. Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended during the initial phase of treatment.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Charcot arthropathy is a progressive condition of the musculoskeletal system that is characterized by joint dislocations, pathologic fractures, and debilitating deformities. It results in progressive destruction of bone and soft tissues at weight-bearing joints. In its most severe form, it may cause significant disruption of the bony architecture.
Charcot arthropathy can occur at any joint; however, it occurs most commonly in the lower extremity, at the foot and ankle. Diabetes is now considered to be the most common aetiology of Charcot arthropathy.

The patient has a non-functioning pituitary tumour as her hormone profile is normal.
Non-functioning pituitary tumours are relatively common. A large number of these tumours are incidentally found pituitary microadenomas (<1 cm) and are usually of no clinical importance.

Indications for surgery for the treatment of primary hyperparathyroidism:
1. Symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation
2. End-organ disease (renal stones, fragility fractures or osteoporosis)
3. An albumin-adjusted serum calcium level of 2.85 mmol/litre or above.

Vit b12 requires trypsin enzyme to split it from its R-binders in order to make the vitamin bind to intrinsic factor required for absorption. In alcoholic patients, chronic pancreatitis is very common. Other causes related to alcoholism can be folate deficiency or bone marrow dysfunction.

In Conn’s syndrome hypokalaemia and hypertension are present due to high levels of aldosterone with normal to high sodium levels. In this disease, the patient presents with hypertension and feelings of tiredness or fatigue.

Hashimoto thyroiditis is the most common cause of hypothyroidism in developed countries. In contrast, worldwide, the most common cause of hypothyroidism is an inadequate dietary intake of iodine. This disease is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis.

Primary hyperaldosteronism, also known as Conn’s Syndrome, is one of the most common causes of secondary hypertension (HTN).
The common clinical scenarios in which the possibility of primary hyperaldosteronism should be considered include the following:
– Patients with spontaneous or unprovoked hypokalaemia, especially if the patient is also hypertensive
– Patients who develop severe and/or persistent hypokalaemia in the setting of low to moderate doses of potassium-wasting diuretics
– Patients with treatment-refractory/-resistant hypertension (HTN)
Patients with severe hypokalaemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalaemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs.

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

Hashimoto thyroiditis is part of the spectrum of autoimmune thyroid diseases (AITDs) and is characterized by the destruction of thyroid cells by various cell- and antibody mediated immune processes. It usually presents with hypothyroidism, insidious in onset, with signs and symptoms slowly progressing over months to years.

The diagnosis of Hashimoto thyroiditis relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features.

The use of hormone replacement therapy (HRT) based on unopposed oestrogen increases the risk of endometrial cancer, and uterine hyperplasia or cancer.
Evidence from randomized controlled studies showed a definite association between HRT and uterine hyperplasia and cancer. HRT based on unopposed oestrogen is associated with this observed risk, which is unlike the increased risk of breast cancer linked with combined rather than unopposed HRT.

Approximately one third of patients treated with radioiodine therapy develop transient hypothyroidism. Unless a patient is highly symptomatic, thyroxine replacement may be withheld if hypothyroidism occurs within the first 2 months of therapy. If it persists for longer than 2 months, permanent hypothyroidism is likely and replacement with T4 should be initiated.

This a case of gestational diabetes presenting with DKA. It is a serious case that requires immediate intervention. Pregnant diabetics tend to develop DKA on a lower serum glucose level than non-pregnant diabetics. The shortness of breath is a trial to wash the excess CO2 to compensate for the metabolic acidosis seen in the ABG. The fruity smell is acetone excreted through the lungs. The main treatment of this case is proper fluid management and insulin infusion.

Selective sodium-glucose transporter-2 (SGLT2) is expressed in the proximal renal tubules and is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen.
Empagliflozin; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion, thus increasing the risk of urinary tract infections.

Klinefelter’s syndrome: The low follicle-stimulating hormone (FSH) and luteinising hormone (LH), together with the low testosterone, suggests a hypogonadotropic hypogonadism. We know that there is no mental retardation, and we are told that physical examination is normal and sense of smell would usually not be tested. Consequently a diagnosis of Kallman’s is suggested. We are not told of a family history of growth delay, thus this is unlikely to be constitutional delay. The thyroid-stimulating hormone (TSH) is normal, making hypothyroidism unlikely and this together with the normal prolactin make hypopituitarism most unlikely.

This patient has polycystic ovarian syndrome (PCOS). Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.
First-line medical therapy usually consists of an oral contraceptive to induce regular menses. The contraceptive not only inhibits ovarian androgen production but also increases sex hormone-binding globulin (SHBG) production. The American College of Obstetricians and Gynaecologists (ACOG) recommends the use of combination low-dose hormonal contraceptive agents for long-term management of menstrual dysfunction.
If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. Pregnancy should be excluded before therapy with oral contraceptives or androgen-blocking agents are started.
First-line treatment for ovulation induction when fertility is desired is clomiphene citrate. Second-line strategies may be equally effective in infertile women with clomiphene citrate-resistant PCOS.

The patient has Acromegaly.
Acromegaly is a chronic disorder characterised by growth hormone (GH) hypersecretion, predominantly caused by a pituitary adenoma.

Random GH level testing is not recommended for diagnosis given the pulsatile nature of secretion. Stress, physical exercise, acute critical illness and fasting state can cause a physiological higher peak in GH secretion.

Pegvisomant is a US Food and Drug Administration-approved treatment for use after surgery. In a global non-interventional safety surveillance study, pegvisomant normalised IGF-1 in 67.5% of patients after 5 years (most likely due to lack of dose-up titration), and also improved clinical symptoms. Pegvisomant improves insulin sensitivity, and long-term follow-up showed significantly decreased fasting glucose over time, while the first-generation SRL only have a marginal clinical impact on glucose homeostasis in acromegaly. Pegvisomant does not have any direct anti-proliferative effects on pituitary tumour cells, but tumour growth is rare overall.

Rotterdam criteria for the diagnosis of polycystic ovary syndrome:
Two of the following three criteria are required:
1. Oligo/anovulation
2. Hyperandrogenism
– Clinical (hirsutism or less commonly male pattern alopecia) or
– Biochemical (raised FAI or free testosterone)
3. Polycystic ovaries on ultrasound
Other aetiologies must be excluded such as congenital adrenal hyperplasia, androgen-secreting tumours, Cushing syndrome, thyroid dysfunction and hyperprolactinaemia.
Cushing’s is excluded because there would have been marked obesity, hypertension and other related features.

The patient is most likely to have Bulimia nervosa. A young girl with a low body mass contributes to the low urea. Hypokalaemia and hyponatraemia are due to vomiting. Her urine sodium is also low.
– In Addison’s diseases, there are low levels of sodium and high levels of potassium in the blood. In acute adrenal crisis: The most consistent finding is elevated blood urea nitrogen (BUN) and creatinine. Urinary and sweat sodium also may be elevated.
– In Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) there is hyponatremia with corresponding hypo-osmolality, continued renal excretion of sodium, urine less than maximally dilute and absence of clinical evidence of volume depletion.

The external laryngeal nerve may be injured or traumatized following thyroid surgery due to its close proximity, which may result in hoarseness or loss of voice.

Sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated.
Organic nitrates and nitric oxide (NO) donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO via increasing cGMP concentrations.

The patient has hyperthyroidism and its most common cause is Grave’s Disease.
Grave’s Disease is an autoimmune disease due to circulating autoantibodies known as TSH receptor stimulating autoantibodies or Thyroid-stimulating immunoglobulins (TSIs) that bind to and activate thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase the synthesis of thyroid hormone.

The patients high morning blood sugar levels are suggestive to Somogyi Phenomenon which suggests that hypoglycaemia during the late evening induced by insulin could cause a counter regulatory hormone response that produces hyperglycaemia in the early morning.
Substitution of regular insulin with an immediate-acting insulin analogue, such as Humulin lispro, may be of some help.

Clinical features are due to excess cortisol. High-dose dexamethasone suppression test shows suppression in patients with Cushing’s disease. Cushing syndrome includes all causes of glucocorticoid excess, whereas Cushing’s disease is reserved only for pituitary-dependent Cushing’s syndrome.

As the patient has early menopause, hormone replacement therapy (HT) is considered to be the first line of choice for prevention of bone loss and fracture in the early postmenopausal period for 5 years.

Oestrogen therapy reduces plasma levels of LDL cholesterol and increases levels of HDL cholesterol. It can improve endothelial vascular function, however, it also has adverse physiological effects, including increasing the plasma levels of triglycerides (small dense LDL particles). Therefore, although HRT may have direct beneficial effects on cardiovascular outcomes, these effects may be reduced or balanced by the adverse physiological effects.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney.
The boy most probably has nephrogenic diabetes insidious (DI) not central DI so he is not responding to the ADH treatment.

The management of patients with diabetes and nephropathy necessitates attention to several aspects of care. Importantly, glycaemic control should be optimized for the patient, attaining the necessary control to reduce complications but done in a safe, monitored manner. Screening for development of nephropathy should be performed on a regular basis to identify microalbuminuria or reductions in GFR and if identified, the diabetes regimen should be tailored accordingly. Prevention and treatment of diabetic nephropathy and other complications necessitates a multifactorial approach. From the options provided insulin is the most suitable as sulfonylureas and biguanides are contraindicated in renal failure. Glitazones are known to cause many side effects including fluid retention and oedema. Hence, insulin will be the best option in this scenario.

Due to the high amount of ADH in their blood, patient is voiding a low volume of urine with high osmolarity and as a result low levels of electrolytes will be present in the serum.

Subacute thyroiditis (De Quervain’s thyroiditis) is a self-limiting thyroid condition presenting with three clinical courses of hyperthyroidism, hypothyroidism, and return to normal thyroid function. In subacute thyroiditis serum thyroglobulin (TG) levels are elevated. ESR is usually greater than 50 mm/h, often exceeding 100 mm/h. Radio-iodine uptake is low or nil. Antithyroperoxidase antibodies are associated with autoimmune thyroiditis

The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.
DiGeorge’s syndrome (DGS) is a developmental abnormality affecting the thymus. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia).

In central and nephrogenic diabetes insipidus (DI), urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality be above 750 mOsm/kg after water deprivation. A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia.

Thyroid malignancies are divided into papillary carcinomas (80%), follicular carcinomas (10%), medullary thyroid carcinomas (5-10%), anaplastic carcinomas (1-2%), primary thyroid lymphomas (rare), and primary thyroid sarcomas (rare).
Hürthle cell carcinoma is a rare thyroid malignancy that is often considered a variant of follicular carcinoma.
– Papillary and Follicular carcinoma are slow-growing tumours
– Sporadic cases of Medullary thyroid carcinoma also typically manifest with painless solitary thyroid nodules in the early stages.
– Anaplastic thyroid carcinoma has the most aggressive biologic behaviour of all thyroid malignancies and has one of the worst survival rates of all malignancies in general. It manifests as a rapidly growing thyroid mass in contrast to a well-differentiated carcinoma, which are comparatively slow-growing. Patients commonly present with associated symptoms due to local invasion. Hoarseness and dyspnoea resulting from the involvement of the recurrent laryngeal nerve and airway occur in as many as 50% of patients.
– Almost all patients with primary thyroid lymphoma have either a clinical history or histological evidence of chronic lymphocytic thyroiditis. The risk of primary thyroid lymphoma increases 70-fold in patients with chronic lymphocytic thyroiditis compared with the general population. Regional and distant lymphadenopathy is common.

Hypocalcaemia presents with such symptoms. It probably happened due to accidental removal of a parathyroid gland during the thyroid surgery. Hypocalcaemia causes laryngospasm which produces stridor.

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH).
GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

Elderly patients with severe hypothyroidism often present with variable symptoms that may be masked or potentiated by co-morbid conditions. Characteristic symptoms may include fatigue, weight gain, cold intolerance, hoarseness, constipation, and myalgias. Neurologic symptoms may include ataxia, depression, and mental status changes ranging from mild confusion to overt dementia.
Clinical findings that may raise suspicion of thyroid hormone deficiency include hypothermia, bradycardia, goitrous enlargement of the thyroid, cool dry skin, myxoedema, delayed relaxation of deep tendon reflexes, a pericardial or abdominal effusion, hyponatremia, and hypercholesterolemia.

The patient has a greatly reduced free T4 concentration, is hypothermic, unconscious and has evidence of associated heart failure. All of those support the diagnosis of profound hypothyroidism.

Exogenous thyroid hormone use has been associated with episodes of thyroid storm as well as thyrotoxic periodic paralysis.
It presents with marked proximal muscle weakness in both upper and lower limbs, hypokalaemia and signs of hyperthyroidism.
Hyperthyroidism generally presents with tachycardia, hypertension, hyperthermia, and cardiac arrhythmias

Laxatives and diuretics can result in electrolyte abnormalities.
Medical complications associated with laxatives include chronic diarrhoea which disrupts the normal stool electrolyte concentrations that then leads to serum electrolyte shifts; acutely, hypokalaemia is most typically seen. The large intestine suffers nerve damage from the chronic laxative use that renders it unable to function properly. The normal peristalsis and conduction are affected; the disorder is thought to be secondary to a degeneration of Auerbach’s Plexi. However, it does not cause muscle weakness.

Insulin tends to cause weight gain, not weight loss.
Metformin does not cause muscle weakness but can cause headaches.

The patient is most likely to have Medullary Thyroid Carcinoma (MTC).
Sporadic, or isolated MTC accounts for 75% of cases and inherited MTC constitutes the rest.
Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occurs.
A 24-hour urinalysis for catecholamine metabolites (e.g., vanillylmandelic acid [VMA], metanephrine) has to be done to rule out concomitant pheochromocytoma in patients with MEN type 2A or 2B, as Pheochromocytoma must be treated before MTC.

The combination of Insulinoma and Parathyroid diseases is suggestive of MEN 1 syndrome.
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumour syndrome inherited in an autosomal dominant manner and characterized by a predisposition to a multitude of endocrine neoplasms primarily of parathyroid, entero-pancreatic, and anterior pituitary origin, as well as non-endocrine neoplasms.
Other endocrine tumours in MEN1 include foregut carcinoid tumours, adrenocortical tumours, and rarely pheochromocytoma. Nonendocrine manifestations include meningiomas and ependymomas, lipomas, angiofibromas, collagenomas, and leiomyomas.

Primary hyperparathyroidism (PHPT), due to parathyroid hyperplasia is the most frequent and usually the earliest expression of MEN-1, with a typical age of onset at 20-25 years.

Once thyrotoxicosis has been identified by laboratory values, the thyroid radio-iodine uptake and scan may be used to help distinguish the underlying aetiology. Thyroid radioiodine uptake is raised in Graves’ disease. It may be normal or raised in patients with a toxic multinodular goitre. It is very low or undetectable in thyrotoxicosis resulting from exogenous administration of thyroid hormone or the thyrotoxic phase of thyroiditis.