A phaeochromocytoma is a rare functional tumour that develops in the adrenal medulla from chromaffin cells. Extra-adrenal paragangliomas (extra-adrenal pheochromocytomas) are tumours that arise in the sympathetic nervous system’s ganglia and are closely connected to extra-adrenal paragangliomas (extra-adrenal pheochromocytomas). Catecholamines are secreted by these tumours, which generate a variety of symptoms and indications associated with sympathetic nervous system hyperactivity.
Hypertension is the most prevalent presenting symptom, which can be continuous or intermittent.

Symptoms are usually intermittent, occurring anywhere from many times a day to occasionally. The symptoms of the condition tend to grow more severe and frequent as the disease progresses.
The ultimate therapy of choice is surgical resection, and if full resection is done without metastases, hypertension is typically cured.

Preoperative medical treatment is critical because it lowers the risk of hypertensive crises during surgery. This is commonly accomplished by combining non-competitive alpha-blockers (such as phenoxybenzamine) with beta-blockers. To allow for blood volume expansion, alpha-blockade should be started at least 7-10 days before surgery. Beta-blockade, which helps to regulate tachycardia and some arrhythmias, can be started after this is accomplished. Hypertensive crises can be triggered if beta-blockade is started too soon.
There should also be genetic counselling, as well as a search for and management of any linked illnesses.

A negative feedback mechanism involving the hypothalamic-pituitary-thyroid axis controls the release of T3 and T4 into the bloodstream.

When metabolic rate is low or serum T3 and/or T4 levels are decrease, this triggers the secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus.

TRH goes to the anterior pituitary gland and stimulates secretion of thyroid-stimulating hormone (TSH).

An increased serum level of T3 and T4 inhibits the release of TRH.

Parathyroid hormone (PTH) is a polypeptide containing 84 amino acids. It is the principal controller of free calcium in the body.
The main actions of parathyroid hormone are:
Increases plasma calcium concentration
Decreases plasma phosphate concentration
Increases osteoclastic activity (increasing calcium and phosphate resorption from bone)
Increases renal tubular reabsorption of calcium
Decreases renal phosphate reabsorption
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)
Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

The anterior pituitary gland produces and secretes a peptide hormone called adrenocorticotropic hormone (ACTH) (adenohypophysis). It is secreted in response to the hypothalamus’s secretion of the hormone corticotropin-releasing hormone (CRH).

ACTH promotes cortisol secretion via binding to cell surface ACTH receptors in the zona fasciculata of the adrenal cortex.

ACTH also promotes the production of beta-endorphin, which is a precursor to melanocyte-releasing hormone (MRH).

Glucagon, a peptide hormone, is produced and secreted by alpha cells of the islets of Langerhans, located in the endocrine portion of the pancreas.

Its main physiological role is stimulation of hepatic glucose output leading to increase in blood glucose. It is the major counter-regulatory hormone to insulin in maintaining glucose homeostasis.

The principal stimulus for the secretion of glucagon is hypoglycaemia. Hypoglycaemia then stimulates:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue leading to increased glycaemia.

Secretion of glucagon is also stimulated by arginine, alanine, adrenaline, acetylcholine and cholecystokinin

Secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Cushing’s syndrome is a collection of symptoms and signs caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids.

The most common cause of Cushing’s syndrome is the iatrogenic administration of corticosteroids. The second most common cause of Cushing’s syndrome is Cushing’s disease.

Cushing’s disease should be distinguished from Cushing’s syndrome and refers to one specific cause of the syndrome, an adenoma of the pituitary gland that secretes large amounts of ACTH and, in turn, elevates cortisol levels. This patient has a diagnosis of Cushing’s disease, and this is, therefore, the underlying cause in this case.

The endogenous causes of Cushing’s syndrome include:
Pituitary adenoma (Cushing’s disease)
Ectopic corticotropin syndrome, e.g. small cell carcinoma of the lung
Adrenal hyperplasia
Adrenal adenoma
Adrenal carcinoma

​Primary hyperparathyroidism the commonest cause of hypercalcaemia. It is commonest in women aged 50 to 60.
The commonest cause of primary hyperparathyroidism is a solitary adenoma of the parathyroid gland (approximately 85% of cases).

Primary hyperparathyroidism may present with features of hypercalcaemia such as polyuria, polydipsia, renal stones, bone and joint pain, constipation, and psychiatric disorders.

In primary Hyperparathyroidism:
PTH is elevated
Calcium is elevated
Phosphate is lowered

In secondary Hyperparathyroidism:
PTH is elevated
Calcium is low or low-normal
Phosphate is raised in CRF

In tertiary Hyperparathyroidism:
PTH is elevated
Calcium is elevated
Phosphate is lowered in CRF

Hypocalcaemia occurs when there is abnormally low level of serum calcium ( >2.2 mmol/l) after correction for the serum albumin concentration.

Rhabdomyolysis causes hyperphosphatemia, and this leads to a reduction in ionised calcium levels.

Patients with rhabdomyolysis are commonly cared for in a high dependency care setting.

Addison’s disease, hyperthyroidism, thiazide diuretics and lithium all cause hypercalcaemia.

A history of recent weight loss is very suggestive of an absolute deficiency of insulin seen in type I diabetes mellitus.

An age of onset of less than 20 years makes a diagnosis of type I diabetes mellitus more likely. However, an increasing number of obese children and young people are being diagnosed with type II diabetes.

Microalbuminuria, peripheral neuropathy, and retinopathy all occur in both type I and type II diabetes mellitus. They are not more suggestive of type I DM.

The adrenal glands produce too little steroid hormones, which causes Addison’s disease. The production of glucocorticoids, mineralocorticoids, and sex steroids are all altered. The most prevalent cause is autoimmune adrenalitis, which accounts for 70-80 percent of cases.

It affects more women than males and occurs most frequently between the ages of 30 and 50.

The following are some of the clinical signs and symptoms of Addison’s disease:

Weakness and sluggishness
Hypotension is a condition in which the blood pressure (notably orthostatic hypotension)
Vomiting and nausea
Loss of weight
Axillary and pubic hair loss
Depression
Hyperpigmentation is a condition in which a person’s (palmar creases, buccal mucosa and exposed areas more commonly affected)
The following are the classic biochemical hallmarks of Addison’s disease:
Hyponatraemia
Hyperkalaemia
Hypercalcaemia
Hypoglycaemia
Acidosis metabolica
When ACTH levels are combined with cortisol levels, it is possible to distinguish between primary and secondary adrenal insufficiency:
In primary insufficiency, levels rise.
In secondary insufficiency, levels are low or low normal.

A thyroid function test is used in the diagnosis of hyperthyroidism.
Serum TSH should be the first-line investigation for patients with suspected hyperthyroidism as it has the highest sensitivity and specificity for hyperthyroidism.

A normal TSH level almost always excludes the diagnosis, though there are rare exceptions to this.

Antithyroglobulin antibodies are commonly present in Graves’ disease, but the test has a sensitivity of 98% and specificity of 99, and is not widely available.

Radioactive iodine uptake scan using iodine-123 – shows low uptake in thyroiditis but high in Graves’ disease and toxic multinodular goitre. It is however, not first-line investigation in this case

Thyroid ultrasound scan – is a cost-effective and safe alternative to the radioactive iodine uptake scan.

Hypothyroidism occurs when there is a deficiency of circulating thyroid hormones. It is commoner in women and is most frequently seen in the age over 60.

Iodine deficiency is the commonest cause of hypothyroidism worldwide.

In developed countries, iodine deficiency is not a problem and autoimmune thyroiditis is the commonest cause.

Hyperthyroidism results from an excess of circulating thyroid hormones. It is commoner in women, and incidence increases with age.

Hyperthyroidism can be subclassified into:
Primary hyperthyroidism – the thyroid gland itself is affected
Secondary hyperthyroidism – the thyroid gland is stimulated by excessive circulating thyroid-stimulating hormone (TSH).

Graves’ disease is the most common cause of hyperthyroidism (estimates are that it causes between 50 and 80% of all cases).

Although toxic multinodular goitre, thyroiditis,TSH-secreting pituitary adenoma and drug-induced hyperthyroidism also causes hyperthyroidism, the commonest cause is Graves’ disease.

A daily calcium intake of 1,000 to 1,300 mg is advised for adults. Women have a slightly higher calcium need than men and are at a higher risk of developing osteoporosis as they age.

Calcium-rich foods include the following:
Milk, cheese, and butter as dairy products.
Broccoli, spinach, and green beans as green veggies.
Bread, rice, and cereals as whole grain foods.
Sardines, salmon, and other bony fish
Eggs
Nuts
The following foods have the least calcium:
Carrot
Fruits such as kiwis, raspberries, oranges, and papaya
Chicken and pork in meats.

Calcium is stored in bones for nearly all of the body’s calcium, but it is also found in some cells (most notably muscle cells) and the blood. The average adult diet comprises roughly 25 mmol of calcium per day, of which the body absorbs only about 5 mmol.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.

A typical biochemical profile can help establish a diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids.

Iatrogenic corticosteroid injection is the most prevalent cause of Cushing’s syndrome.
Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater throughout the 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed.

Insulin resistance causes hyperglycaemia, which is a frequent symptom. Insulin resistance can produce acanthosis nigricans in the axilla and around the neck, as well as other skin abnormalities.

In contrast to menorrhagia, elevated testosterone levels are more likely to produce amenorrhoea or oligomenorrhoea. Infertility in women of reproductive age can also be caused by high androgen levels.

A dexamethasone suppression test or a 24-hour urine free cortisol collection can both be used to establish the existence of Cushing’s syndrome.

Hypothyroidism is diagnosed using the results of thyroid function tests (TFTs).

In the early stages of the disease, the earliest biochemical change noticed is a rise in thyroid-stimulating hormone (TSH) levels. Free triiodothyronine (T3) and thyroxine (T4) levels are usually normal.

In primary hypothyroidism, the serum TSH level is usually greater than 10 mU/L, and free T4 levels are below the reference range.

Subclinical hypothyroidism is diagnosed when the serum TSH level is above the reference range, and the free T4 levels are within the reference range. The test should, however, be repeated after 3-6 months to exclude transient causes of raised TSH.

In summary, how to interpret TFTs in cases of suspected hypothyroidism is shown below:

Subclinical hypothyroidism
TSH is raised
Free T4 is normal
Free T3 is normal

Primary hypothyroidism
TSH is raised
Free T4 is lowered
Free T3 is lowered or normal

Secondary hypothyroidism
TSH is lowered or normal
Free T4 is lowered
Free T3 is lowered or normal

Only a very small fraction of the thyroid hormones circulating in the blood are free. The majority is bound to transport proteins. Only the free thyroid hormones are biologically active, and measurement of total thyroid hormone levels can be misleading.

The relative percentages of bound and unbound thyroid hormones are:
Bound to thyroid-binding globulin -70%
Bound to albumin -15-20%
Bound to transthyretin -10-15%
Free T3 -0.3%
Free T4 -0.03%

When there are excessive circulating levels of aldosterone, hyperaldosteronism occurs. There are two main types of hyperaldosteronism:

Primary hyperaldosteronism (,95% of cases)
Secondary hyperaldosteronism (,5% of cases)

Primary causes of hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome)
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism
Secondary causes of hyperaldosteronism include:
Drugs
Obstructive renal artery disease
Renal vasoconstriction
Oedematous disorders syndrome

Adrenal adenoma is the commonest cause of hyperaldosteronism (seen in ,80% of all cases).

Insulin receptor (IR), in addition to being activated by insulin, is also activated by IGF-I and IGF-II.

The IR is a dimer with two identical subunits spanning the cell membrane and are connected by a single disulphide bond. The two sub-units include: The alpha chain situated on the exterior of the cell membrane and the beta chain spanning the cell membrane in a single segment.

When insulin is detected, the alpha chains move together folding around the insulin making the beta chains move together, converting them into an active tyrosine kinase. This initiates a phosphorylation cascade increasing the expression of GLUT4 and allowing uptake of glucose by cells.

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Parathyroid hormone (PTH), a polypeptide containing 84 amino acids, is the principal hormone that controls free calcium in the body.

Its main actions are:
Increases osteoclastic activity
Increases plasma calcium concentration
Decreases renal phosphate reabsorption
Decreases plasma phosphate concentration
Increases renal tubular reabsorption of calcium
Increases calcium and phosphate absorption in the small intestine
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol

Corticotropin-releasing hormone (CRH) is a neurotransmitter and peptide hormone. It is generated by cells in the hypothalamic paraventricular nucleus (PVN) and released into the hypothalamo-hypophyseal portal system at the median eminence through neurosecretory terminals of these neurons. Stress causes the release of CRH.

The CRH is carried to the anterior pituitary through the hypothalamo-hypophyseal portal system, where it activates corticotrophs to release adrenocorticotropic hormone (ACTH). Cortisol, glucocorticoids, mineralocorticoids, and DHEA are all produced in response to ACTH.

Excessive CRH production causes the size and quantity of corticotrophs in the anterior pituitary to expand, which can lead to the creation of a corticotrope tumour that generates too much ACTH.

When there are excessive levels of aldosterone independent of the renin-angiotensin aldosterone axis, primary hyperaldosteronism occurs. Secondary hyperaldosteronism occurs due to high renin levels.

Causes of primary hyperaldosteronism include:
Conn’s syndrome
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism

Causes of secondary hyperaldosteronism include:
Renal vasoconstriction
Oedematous disorders
Drugs – diuretics
Obstructive renal artery disease

Although patients are usually asymptomatic, when clinical features are present, classically hyperaldosteronism presents with:
Hypokalaemia
Sodium levels can be normal or slightly raised
Hypertension
Metabolic alkalosis
Less common, clinical features are:
Lethargy
Headaches
Intermittent paraesthesia
Polyuria and polydipsia
Muscle weakness (from persistent hypokalaemia)
Tetany and paralysis (rare)

Osteoclasts are a type of bone cell that breaks down bone tissue. This is a critical function in the maintenance, repair and remodelling of bones. The osteoclast disassembles and digests the composite of hydrated protein and minerals at a molecular level by secreting acid and collagenase. This process is known as bone resorption and also helps to regulate the plasma calcium concentration.
Osteoclastic activity is controlled by a number of hormones:
1,25-dihydroxycholecalciferol increases osteoclastic activity
Parathyroid hormone increases osteoclastic activity
Calcitonin inhibits osteoclastic activity
Bisphosphonates are a class of drug that slow down and prevent bone damage. They are osteoclast inhibitors.

The only mechanism by which insulin facilitates uptake of glucose into cells is by facilitated diffusion through a family of hexose transporters.

The major transporter used for glucose uptake is GLUT4. GLUT4 is made available in the plasma membrane by the action of insulin.
When insulin concentrations are low, GLUT4 transporters are present in cytoplasmic vesicles, where they are cannot be used for transporting glucose.

Insulin is produced by beta cells, located centrally within the islets of Langerhans, in the endocrine tissues of the pancreas. Insulin is a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds. Proinsulin is synthesised as a single-chain peptide. Within storage granules, a connecting peptide (C peptide) is removed by proteases to yield insulin. Insulin release is stimulated initially during eating by the parasympathetic nervous system and gut hormones such as secretin, but most output is driven by the rise in plasma glucose concentration that occurs after a meal. The effects of insulin are mediated by the receptor tyrosine kinase.

Parathyroid hormone (PTH) is a polypeptide containing 84 amino acids. It is the principal controller of free calcium in the body.
PTH is synthesised by and released from the chief cells of the four parathyroid glands that are located immediately behind the thyroid gland.
PTH is released in response to the following stimuli:
Decreased plasma calcium concentration
Increased plasma phosphate concentration (indirectly by binding to plasma calcium and reducing the calcium concentration)
PTH release is inhibited by the following factors:
Normal/increased plasma calcium concentration
Hypomagnesaemia
The main actions of PTH are:
Increases plasma calcium concentration
Decreases plasma phosphate concentration
Increases osteoclastic activity (increasing calcium and phosphate resorption from bone)
Increases renal tubular reabsorption of calcium
Decreases renal phosphate reabsorption
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)
Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)