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.

Cushing’s syndrome has a wide range of clinical manifestations that are dependent on the degree of cortisol overproduction. The appearance might be vague and the diagnosis difficult to detect when cortisol levels are just somewhat elevated. On the other hand, in long-term cases of severely increased cortisol levels, the presentation might be colourful and the diagnosis simple.

Cushing’s syndrome has the following clinical features:
Obesity and weight growth in the true sense
Supraclavicular fat pads are fat pads that are located above the clavicle.
Buffalo hump
Fullness and plethora of the face (‘moon facies’)
Muscle atrophy and weakening at the proximal level
Diabetes mellitus, also known as impaired glucose tolerance
Hypertension
Skin thinning and bruising
Depression
Hirsutism
Acne
Osteoporosis
Amenorrhoea or oligomenorrhoea

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 during the whole 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed. As a result, random cortisol testing is not an effective screening technique and is not advised.

The following are the two most common first-line screening tests:
Cortisol levels in the urine are measured every 24 hours.
A diagnosis of Cushing’s syndrome can be made if more than two collections measure cortisol excretion more than three times the upper limit of normal.
Physical stress (e.g., excessive exercise, trauma), mental stress (e.g., sadness), alcohol or drug misuse, complex diabetes, and pregnancy can all cause false positives.
Renal dysfunction, inadequate collection, and cyclical Cushing’s disease can all cause false negatives.
The overnight low-dose dexamethasone suppression test (LDDST) involves giving 1 mg of dexamethasone at 11 p.m. and measuring blood cortisol levels at 8 a.m. the next day.
Cushing’s syndrome is diagnosed when cortisol is not suppressed to less than 50 nmol/L.
It might be difficult to tell the difference between mild Cushing’s disease and normal cortisol production.
False positives can occur as a result of depression, severe systemic sickness, renal failure, prolonged alcohol misuse, old age, and the use of hepatic enzyme-inducing medicines, among other things.
False negatives are extremely uncommon in Cushing’s disease patients.

A characteristic biochemical picture might also be helpful in confirming the diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

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

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.

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.

​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

The hormone-active metabolite of vitamin D is 1,25-dihydroxycholecalciferol (commonly known as calcitriol). Its activities raise calcium and phosphate levels in the bloodstream.

The following are the primary effects of 1,25-dihydroxycholecalciferol:

Calcium and phosphate absorption in the small intestine is increased.
Calcium reabsorption in the kidneys is increased.
Increases phosphate reabsorption in the kidneys.
Increases the action of osteoclastic bacteria (increasing calcium and phosphate resorption from bone)
Inhibits the action of 1-alpha-hydroxylase in the kidneys (negative feedback)
Thyroid hormone (parathyroid hormone) Calcium reabsorption in the tubules of the kidneys is increased, but renal phosphate reabsorption is decreased.

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.

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

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.

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)

Insulin, a peptide hormone, is produced in the pancreas by the beta-cells of the islets of Langerhans.

The beta-cells first synthesise an inactive precursor called preproinsulin which is converted to proinsulin by signal peptidases, which remove a signal peptide from the N-terminus.

Proinsulin is converted to insulin by the removal of the C-peptide.

Insulin has a short half-life in the circulation of about 5-10 minutes.
Glucagon and parasympathetic stimulation stimulates insulin release.

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

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.

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)

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.

Hormones can be classified into three categories depending on their chemical composition: amines, peptides (and proteins), and steroids. Amines are made up of single amino acids (for example, tyrosine), peptide hormones are made up of peptides (or proteins), and steroid hormones are made up of cholesterol.
The table below lists some prominent instances of each of these three hormone classes:

1. Peptide hormone:
Adrenocorticotropic hormone (ACTH)
Prolactin
Vasopressin
Oxytocin
Glucagon
Insulin
Somatostatin
Cholecystokinin

2. Amine hormone:
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)
Dopamine

3. Steroid hormone:
Mineralocorticoids (e.g. aldosterone)
Glucocorticoids (e.g. cortisol)
Progestogens
Androgens
Oestrogens

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.

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.

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

1-alpha-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney.

The key regulatory point in the formation of 1,25-dihydroxycholecalciferol is 1-alpha-hydroxylase, which is promoted by parathyroid hormone or hypophosphatemia.

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 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. Cushing’s illness is the second most prevalent cause of Cushing’s syndrome. Cushing’s disease is distinct from Cushing’s syndrome in that it refers to a single cause of the illness, a pituitary adenoma that secretes high quantities of ACTH, which raises cortisol levels.

Because cortisol enhances the vasoconstrictive impact of endogenous adrenaline, patients with Cushing’s syndrome are usually hypertensive.

Hyperglycaemia (due to insulin resistance) rather than hypoglycaemia is a common symptom.
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.

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 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.

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.

Glucagon, secreted from the pancreatic islet alpha cells, is considered to be the main catabolic hormone of the body. It raises the concentration of glucose and fat in the bloodstream

There are five different pancreatic islet cells:
Alpha cells (20%) – produce glucagon
Beta cells (70%) – produce insulin and amylin
Delta cells (<10%) – produce somatostatin
Gamma cells (<5%) – produce pancreatic polypeptide
Epsilon cells (<1%) – produce ghrelin

Approximately half of total serum calcium is in the free or ionised Ca2+ state, 40% is attached to plasma proteins (mostly albumin), and the remaining 10% is in complexes with organic ions like citrate and phosphate. The ionized form is the only one that works.

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.

PTH is synthesised and released from the chief cells of the four parathyroid glands located behind the thyroid gland.
It is a polypeptide containing 84 amino acids and it controls free calcium in the body.

The following stimuli causes release of PTH:
Increased plasma phosphate concentration
Decreased plasma calcium concentration

PTH release is inhibited by:
Normal or 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)

Insulin is an anabolic hormone. Its actions can be broadly divided into:
Lipid metabolism
Protein metabolism and
Carbohydrate metabolism

For lipid metabolism, insulin:
Stimulates lipogenesis
Inhibits lipolysis by lipase

For carbohydrate metabolism, insulin:
Decreases gluconeogenesis
Stimulates glycolysis
Promotes glucose uptake in muscle and adipose tissue
Promotes glycogen storage
Increases glycogenesis
Decreases glycogenolysis

Protein metabolism:
Stimulates protein synthesis
Accelerates net formation of protein
Stimulates amino acid uptake
Inhibits protein degradation
Inhibits amino acid conversion to glucose