The earliest biochemical change seen in hypothyroidism is an increase in thyroid-stimulating hormone (TSH) levels.

Triiodothyronine (T3) and thyroxine (T4) levels are normal in the early stages.

TBG levels are generally unchanged in primary hypothyroidism.

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.

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.

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

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.

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.

Cushing’s syndrome has several endogenous sources, including:
Cushing’s disease is caused by a pituitary adenoma.
Adrenal adenoma Ectopic corticotropin syndrome, e.g. small cell cancer of the lung
Adrenal carcinoma is a cancer of the adrenal gland.
Hyperplasia of the adrenal glands

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

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.

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)

Primary hyperaldosteronism occurs when there are excessive levels of aldosterone independent of the renin-angiotensin axis. Secondary hyperaldosteronism occurs due to high renin levels.
The causes of primary hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome) – the most common cause of hyperaldosteronism (,80% of all cases). These are usually unilateral and solitary and are more common in women.
Adrenal hyperplasia – this accounts for ,15% of all cases. Usually, bilateral adrenal hyperplasia (BAH) but can be unilateral rarely. More common in men than women.
Adrenal cancer – a rare diagnosis but essential not to miss
Familial aldosteronism – a rare group of inherited conditions affecting the adrenal glands
The causes of secondary hyperaldosteronism include:
Drugs – diuretics
Obstructive renal artery disease – renal artery stenosis and atheroma
Renal vasoconstriction – occurs in accelerated hypertension
Oedematous disorders – heart failure, cirrhosis and nephrotic syndrome
Patients are often asymptomatic. When clinical features are present, the classically described presentation of hyperaldosteronism is with:
Hypertension
Hypokalaemia
Metabolic alkalosis
Sodium levels can be normal or slightly raised
Other, less common, clinical features include:
Lethargy
Headaches
Muscle weakness (from persistent hypokalaemia)
Polyuria and polydipsia
Intermittent paraesthesia
Tetany and paralysis (rare)
Often the earliest sign of hyperaldosteronism is from aberrant urea and electrolytes showing hypokalaemia and mild hypernatraemia. If the patient is taking diuretics, and the diagnosis is suspected, these should be repeated after the patient has taken off diuretics.
If the diagnosis is suspected, plasma renin and aldosterone levels should be checked. Low renin and high aldosterone levels (with a raised aldosterone: renin ratio) is suggestive of primary aldosteronism.
If the renin: aldosterone ratio is high, then the effect of posture on renin, aldosterone and cortisol can be investigated to provide further information about the underlying cause of primary hyperaldosteronism. Levels should be measured lying at 9 am and standing at noon:
If aldosterone and cortisol levels fall on standing, this is suggestive of an ACTH dependent cause, e.g. adrenal adenoma (Conn’s syndrome)
If aldosterone levels rise and cortisol levels fall on standing, this is suggestive of an angiotensin-II dependent cause, e.g. BAH
Other investigations that can help to distinguish between an adrenal adenoma and adrenal hyperplasia include:
CT scan
MRI scan
Selective adrenal venous sampling

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.

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.

Glucagon binds to class B G-protein coupled receptors and activates adenylate cyclase, increasing cAMP intracellularly.

This activates protein kinase A. Protein kinase A phosphorylates and activates important enzymes in target cells.

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).

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.

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.

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

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

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.

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. 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

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.

Dopamine is a neurotransmitter and amine hormone that is derived from the amino acid tyrosine. It is made in a number of places throughout the human body, both inside and outside the central nervous system. The adrenal medulla, dopamine neurons in the arcuate nucleus of the hypothalamus, the substantia nigra, and other areas of the brain produce dopamine.

The tuberoinfundibular pathway refers to the dopamine neurons in the arcuate nucleus of the hypothalamus’ tubeal region. Dopamine is discharged into the hypothalamo-hypophyseal portal system from these neurons’ neurosecretory terminals at the median eminence.

The major function of dopamine produced from the hypothalamus is to suppress prolactin production from the anterior pituitary, and it is released in reaction to excessive levels of prolactin secretion. Modulation of motor-control centres and activation of reward centres are two more crucial activities of the brain.
Dopamine-secreting cells can also be found in other areas of the body, where they perform mostly paracrine functions (acting on nearby cells).

Although Addisonian crisis is a rare illness, it can be fatal if it is misdiagnosed. Hypoglycaemia and shock are the most common symptoms of an Addisonian crisis (tachycardia, peripheral vasoconstriction, hypotension, altered conscious level, and coma).

Other clinical characteristics that may be present are:
Fever
Psychosis
Leg and abdominal pain
Dehydration and vomiting
Convulsions 

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.

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.

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.

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.

In the presence of UVB light, 7-dehydrocholesterol is converted to cholecalciferol in the epidermal layer of the skin, resulting in 1,25-dihydroxycholecalciferol.

Cholecalciferol is then converted to 25-hydroxycholecalciferol in the endoplasmic reticulum of liver hepatocytes by 25-hydroxylase (calcifediol).

Finally, 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 induced by parathyroid hormone or hypophosphatemia.

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)