The anterior pituitary gland (adenohypophysis or pars distalis) synthesizes and secretes:

1. FSH (follicle-stimulating hormone)

2. LH (luteinizing hormone)

3. Growth hormone

4. Prolactin

5. ACTH (adrenocorticotropic hormone)

6. TSH (thyroid-stimulating hormone).

The posterior pituitary gland (neurohypophysis) stores and secretes 2 hormones produced by the hypothalamus:

1. ADH (antidiuretic hormone or vasopressin)

2. Oxytocin

Excess of circulating free thyroid hormones (thyroxine and/or triiodothyronine) leads to hyperthyroidism. Common causes include Graves’ disease, toxic thyroid adenoma and toxic multinodular goitre. Grave’s disease is the most common cause and is responsible for 70-80% cases of hyperthyroidism. Other causes include excess intake of thyroid hormone, amiodarone-related. It is important that hyperthyroidism is not confused with hyperthyroxinaemia (high levels of thyroid hormone in blood), which includes causes like thyroiditis. Both the conditions lead to thyrotoxicosis (symptoms due to hyperthyroxinemia). Symptoms include weight loss associated with increased appetite, anxiety, weakness, heat intolerance, depression, increased sweating, dyspnoea, loss of libido, diarrhoea, palpitations and occasionally arrhythmias. If there is an acute increase in metabolic rate, the condition is known as ‘thyroid storm’. Elderly sometimes present only with fatigue and weight loss and this is called apathetic hyperthyroidism. Neurological symptoms are also seen in hyperthyroidism and these are tremor, chorea, myopathy and periodic paralysis. One of the most serious complications of hyperthyroidism is stroke of cardioembolic origin due to coexisting atrial fibrillation.

Insulin is produced by the beta-cells of the islets of Langerhans in the pancreas. Its actions include:

– promoting uptake of glucose into cells

– glycogen synthesis (glycogenesis)

– protein synthesis

– stimulation of lipogenesis (fat formation).

– driving potassium into cells – used to treat hyperkaelamia.

Parathyroid hormone and activated vitamin D are the principal hormones involved in calcium/phosphate metabolism, rather than insulin.

Total thyroidectomy might sometimes result in inadvertent excision or damage of parathyroid glands, leading to hypoparathyroidism. Monitoring serum calcium levels in the post-operative period to detect hypocalcaemia is essential to diagnose and prevent this condition.

MEN (Multiple Endocrine Neoplasia) syndromes are a group of three separate familial disease which consists of adenomatous hyperplasia and neoplasia in several endocrine glands. All three conditions are inherited as an autosomal dominant trait, with a single gene producing multiple effects. MEN IIA is characterized by medullary carcinoma of the thyroid, pheochromocytoma and hyperparathyroidism. It should be suspected in patients with bilateral pheochromocytoma, a familial history of MEN, or at least two characteristic endocrine manifestations. Genetic testing is used to confirm the diagnosis. Early diagnosis is crucial to aid in complete excision of the localized tumour. Pheochromocytomas can be detected by plasma free metanephrines and fractionated urinary catecholamines, particularly adrenaline (epinephrine).

Imaging studies such as computed tomography or magnetic resonance imaging might also prove useful. Hyperparathyroidism is diagnosed by the standard finding of hypercalcaemia, hypophosphatemia and an increased parathyroid hormone level. Once MEN IIA syndrome is identified in any patient, it is recommended that his or her first-degree relatives and any other symptomatic also undergo genetic testing. Relatives should be subjected to annual screening for hyperparathyroidism and pheochromocytoma beginning in early childhood and continue indefinitely. Serum calcium levels help in screening for hyperparathyroidism. Similarly, screening for pheochromocytoma is by history, measurement of the blood pressure and laboratory testing.

When the parathyroid glands secrete excess parathyroid hormone (PTH) in response to hypocalcaemia, it is known as Secondary hyperparathyroidism and is often seen in patients with renal failure. In chronic renal failure, the kidneys fail to excrete adequate phosphorus and also fail to convert enough vitamin D to its active form. This leads to formation of insoluble calcium phosphate in the body which ultimately causes hypocalcaemia. The glands then undergo hyperplasia and hypertrophy leading to secondary hyperparathyroidism. Symptoms include bone and joint pains, along with limb deformities. The raised PTH also results in pleiotropic effects on blood, the immune system and nervous system.

The adrenal gland comprises an outer cortex and an inner medulla, which represent two developmentally and functionally independent endocrine glands.

The adrenal medulla secretes adrenaline (70%) and noradrenaline (30%)

The adrenal cortex consists of three layers (remembered by the mnemonic GFR):

G = zona glomerulosa – secretes aldosterone

F = zona fasciculata – secretes cortisol and sex steroids

R = zona reticularis – secretes cortisol and sex steroids.

Aldosterone facilitates the reabsorption of sodium and water and the excretion of potassium and hydrogen ions from the distal convoluted tubule and collecting ducts. Conn’s syndrome is characterized by increased aldosterone secretion from the adrenal glands.

Excessively high levels of prolactin in the blood is called hyperprolactinaemia. Normally, prolactin levels are less than 580 mIU/l in females and less than 450 mIU/l in men. The biologically inactive macroprolactin can lead to a false high reading. However, the patient remains asymptomatic. Dopamine down-regulates prolactin whereas oestrogen upregulates it. Hyperprolactinaemia can be caused due to lack of inhibition (compression of pituitary stalk or low dopamine levels), or increased production due to a pituitary adenoma (prolactinoma). Either of these causes can lead to a prolactin level of 1000-5000 mIU/l. However, levels more than 5000mIU/l are usually associated due to an adenoma and >100,000 mIU/l are seen in macroadenomas (tumours < 1cm in diameter). Increased prolactin causes increased dopamine release from the arcuate nucleus of hypothalamus. This increased dopamine in turn, inhibits the GnRH (Gonadotrophin Releasing Hormone) thus blocking gonadal steroidogenesis resulting in the symptoms of hyperprolactinaemia. In women, it includes hypoestrogenism, anovulatory infertility, decreased or irregular menstruation or complete amenorrhoea. It can even cause production of breast milk, loss of libido, vaginal dryness and osteoporosis. In men, the symptoms include impotence, decreased libido, erectile dysfunction and infertility. In men, treatment can be delayed due to late diagnosis as they have no reliable indicator such as menstruation that might indicate a problem. Most of the male patients seek help only when headaches and visual defects start to surface.

A neuroendocrine tumour of the chromaffin cells in adrenal medulla, pheochromocytoma secretes excessive catecholamines – adrenaline (epinephrine) and noradrenaline (norepinephrine). Pheochromocytomas are also known as the ‘10% tumour’. This is because 10% of them are bilateral, 10% are malignant, and 10% are extra-adrenal. Extra-adrenal paragangliomas (also known as extra-adrenal pheochromocytomas) are less common than pheochromocytomas and arise in the ganglia of sympathetic nervous system. Around 25% of pheochromocytomas are familial. Symptoms are described as feeling of ‘impending doom’, and include tachycardia, hypertension, palpitations, anxiety, headaches and pallor. Orthostatic hypertension is typically seen where there is a more than 100 mmHg fall in systolic pressure when the patient stands up. Pheochromocytomas can also lead to malignant hypertension. Diagnosis is by measurement of catecholamines and metanephrines in blood or in 24-hour urine, after exclusion of other possible causes such as stress, hypoglycaemia and drugs (methyldopa, dopamine agonists, ganglion-blocking antihypertensive). Imaging is also needed to localize the tumour. Localization of the tumour can also be done by Iodine-131 meta-iodobenzylguanidine (I131-MIBG) imaging.

Thyroglossal cyst is the most common congenital thyroid anomaly which is clinically significant and affects women more than men. It is a vestigial remnant of developing thyroid. Although the thyroglossal cyst can develop anywhere along the thyroglossal duct, the most common site is in the midline between the isthmus of thyroid and hyoid bone, or just above the hyoid. Thyroglossal cysts are also associated with ectopic thyroid tissue. Clinically, the cyst moves upward with protrusion of the tongue. Rarely, the persistent duct can become malignant (thyroglossal duct carcinoma) where the cancerous cells arise in the ectopic thyroid tissue that are deposited along the duct. Exposure to radiation is a predisposing factor.

Prolactinoma is the mot common pituitary adenoma; leading to hyperprolactinaemia. By virtue of their size, macroprolactinomas press on the adjacent structures leading to headaches and loss of vision due to the pressure effect on optic chiasm. Women notice a change in their menstrual cycle due to raised prolactin levels. In comparison, the problem goes unnoticed in men in the initial stages. Craniopharyngioma is a less common space-occupying lesions affecting children and young adults.

Craniopharyngiomas (also known as Rathke pouch tumours, adamantinomas or hypophyseal duct tumours) affect children mainly between the age of 5 and 10 years. It constitutes 9% of brain tumours affecting the paediatric population. These are slow-growing tumours which can also be cystic, and arise from the pituitary stalk, specifically the nests of epithelium derived from Rathke’s pouch. Histologically, this tumour shows nests of squamous epithelium which is lined on the outside by radially arranged cells. Calcium deposition is often seen with a papillary type of architecture.

ACTH-secreting pituitary adenomas are rare and mostly microadenomas. Paediatric astrocytoma’s usually occur in the posterior fossa. Although null cell adenomas can cause mass effect and give rise to the described symptoms, they are not suprasellar. Prolactinomas can also show symptoms of headache and disturbances in the visual field, however they are known to be small and slow-growing.

The symptoms suggest Cushing syndrome due to increased glucocorticoid levels. One cause of Cushing syndrome is ectopic production of adrenocorticotrophic hormone from oat cell carcinoma. As oat cell carcinoma is known to be highly metastatic, the tenderness in lower back could represent metastatic involvement.

The lymphatic drainage of an organ is related to its blood supply. The lymphatic drainage of the testis drains along the testicular artery to reach the lymph nodes along the aorta.

Tyrosine is the precursor to adrenaline, noradrenaline and dopamine. Tyrosine hydroxylase converts tyrosine to DOPA, which is in turn converted to dopamine, then to noradrenaline and finally adrenaline.

Adrenocortical carcinomas are rare tumours with reported incidence being only two in a million. However, they have a poor prognosis. These are large tumours and range from 4-10 cm in diameter. They arise from the adrenal cortex and 10% cases are bilateral. 50-80% are known to be functional, leading to Cushing syndrome. Even though the tumour affects both sexes equally, functional tumours are slightly commoner in women and non-functional tumours are commoner in men. As compared to women, men also develop this tumour at an older age and seem to have a poorer prognosis.

Hypercalcaemia with hypophosphatemia indicates parathyroid disorder and adenomas are more common than hyperplasia. In this young age group, metastatic disease is unlikely. Solitary adenomas are responsible for 80-85% cases of primary hyperparathyroidism. 10-15% cases are due to parathyroid hyperplasia and carcinomas account for 2-3% cases. Symptoms include bone pain (bones), nephrolithiasis (stones), muscular aches, peptic ulcer disease, pancreatitis (groans), depression (moans), anxiety and other mental disturbances.

Overproduction of aldosterone (a mineralocorticoid) by the adrenal glands is known as Conn’s syndrome. It can be either due to an aldosterone-secreting adrenal adenoma (50-60% cases) or adrenal gland hyperplasia (40-50% cases). Excess aldosterone leads to sodium and water retention, along with potassium excretion. This leads to arterial (non-essential) hypertension. Conn’s syndrome is the commonest cause of primary hyperaldosteronism. Other symptoms include muscle cramps, headache (due to hypokalaemia) and metabolic alkalosis, which occurs due to increased secretion of H+ ions by the kidney. The raised pH of the blood traps calcium leading to symptoms of hypocalcaemia, which can be mimicked by liquorice ingestion and Liddle syndrome. To diagnose Conn’s syndrome, the ratio of renin and aldosterone is measured. Due to suppression of renin secretion, there is low renin to aldosterone ratio (<0.05). However, anti-hypertensives may affect the test results and should be withdrawn for 6 weeks. Computed tomography can also be done to detect the presence of adrenal adenoma. Cushing’s syndrome does not cause hypokalaemia with normal serum glucose levels. Nelson’s syndrome refers to increased ACTH secretion due to pituitary adenoma. Pheochromocytoma will not lead to hypokalaemia even though hypertension can be seen.

Papillary carcinoma accounts for 70-80% of all thyroid cancers and is seen commonly in people aged 30-60 years. It is more aggressive in elderly patients. 10-20% cases may have recurrence or persistent disease. More common in females with a female to male ratio of 3:1. Papillary carcinomas can also contain follicular carcinomas. The common route of spread is through lymphatics to regional nodes in one-third cases and pulmonary metastasis can also occur. Papillary carcinomas of the thyroid have the best prognosis, especially in patients less than 45 years of age with small tumours confined to the thyroid gland.

Findings described are suggestive of Waterhouse-Friderichsen syndrome which develops secondary to meningococcaemia. The reported incidence of Addison’s disease is 4 in 100,000. It affects both sexes equally and is seen in all age groups. It tends to show clinical symptoms at the time of metabolic stress or trauma. The symptoms are precipitated by acute infections, trauma, surgery or sodium loss due to excessive perspiration.