HypoT & P

Question 1

What’s the Location and Function of the Hypothalamus?

Answer 1

The hypothalamus is a part of the brain situated on its ventral (bottom) surface, around the third ventricle (a fluid-filled cavity in the brain).

Its main role is to control the secretion of hormones from the pituitary gland.

Question 2

Explain the Synthesis and Transport of hormones released from the pst pituitary gland

Answer 2

Synthesis and Transport:

These hormones are synthesized in the hypothalamus.

They travel down nerve fibers (part of the pituitary stalk) attached to carrier proteins called neurophysins.

The hormones are stored in the posterior pituitary gland and released into the bloodstream when needed, along with neurophysin.

Neurophysin itself does not have a biological function and is quickly removed from the blood.

Question 3

Where’s ADH produced and it’s primary function

Answer 3

Mainly produced in the supraoptic nuclei of the hypothalamus.

Its primary role is to help the kidneys reabsorb water from the collecting ducts, thus conserving water in the body

Question 4

Where’s oxytocin produced and it’s primary function

Answer 4

Mainly produced in the paraventricular nuclei of the hypothalamus.

It controls the ejection of milk from the breast during lactation.

It may also help initiate uterine contractions during childbirth, although labor can still proceed without it.

Oxytocin can be used medically to induce labor.

Question 5

The hypothalamus releases peptide hormones, also known as hypothalamic-releasing hormones.
These hormones can be released in two ways:

Answer 5

Directly to the Anterior Pituitary: Via a special blood vessel system called the short private portal system (e.g., TRH - Thyrotropin-releasing hormone, GnRH - Gonadotropin-releasing hormone).

Into General Circulation: Directly into the bloodstream (e.g., oxytocin and vasopressin). attached to carrier proteins called neurophysins.

Question 6

Neurophysins and Neural Pathways

Neurophysins:

Oxytocin and vasopressin are produced in the hypothalamus and travel down nerve fibers to the posterior pituitary gland.

During this journey, they are bound to carrier proteins known as neurophysins.

Neurophysins help transport these hormones to the posterior pituitary, where they are stored until needed.

When released into the bloodstream, neurophysins are also released but do not have any biological function and are quickly cleared from the blood.

Question 7

Explain the Connection Between Hypothalamus and Anterior Pituitary

Answer 7

No Direct Neural Connection: Unlike the posterior pituitary, the anterior pituitary gland is not directly connected to the hypothalamus via nerves.
Hypothalamic Portal System: The hypothalamus produces regulating hormones (small molecules) that travel to the anterior pituitary through a specialized blood vessel system known as the hypothalamic portal system.

Question 8

Explain How the Hypothalamic Portal System Works

Answer 8

First Capillary Network: The hypothalamic hormones enter the blood through capillaries in the median eminence of the hypothalamus.

Veins: These capillaries form veins that pass down the pituitary stalk.

Second Capillary Network: The veins then divide into a second network of capillaries in the anterior pituitary gland.

Stimulation or Inhibition: The hypothalamic hormones released into this second capillary network stimulate or inhibit the secretion of anterior pituitary hormones into the systemic circulation.

Question 9

Explain the Cell Types and Hormones located in the anterior Pituitary lobe & their function

Answer 9

Cell Types and Hormones:

Acidophils
(lactotrophs and somatotrophs) secrete prolactin and GH, affecting peripheral tissues directly.

Basophils secrete hormones that regulate other endocrine glands.

Corticotrophs:

Hormones Produced: Corticotrophs synthesize a large polypeptide called pro-opiomelanocortin (POMC). POMC is a precursor that is split into two main hormones:

Adrenocorticotropic Hormone (ACTH or Corticotrophin)

β-Lipotropin (β-LPH)

Functions of ACTH:

Stimulates Adrenal Cortex: ACTH promotes the synthesis and secretion of steroids (except aldosterone) from the adrenal cortex.

Maintains Adrenal Growth: It helps maintain the growth of the adrenal cortex.

Melanocyte-Stimulating Activity: High levels of ACTH can increase pigmentation of the skin.

Functions of β-Lipotropin:

Inactive Until Conversion: β-Lipotropin is inactive until it is converted into endorphins.

Endorphins: These neurotransmitters have opiate-like effects that help control pain.

Gonadotrophs:

Hormones Produced: Gonadotrophs secrete gonadotropins, which include:

Follicle-Stimulating Hormone (FSH)

Luteinizing Hormone (LH)

Functions of FSH and LH:

FSH: Stimulates the growth of ovarian follicles in females and spermatogenesis in males.

LH: Triggers ovulation and the formation of the corpus luteum in females and stimulates testosterone production in males.

Thyrotrophs:

Hormone Produced: Thyrotrophs secrete Thyroid-Stimulating Hormone (TSH or Thyrotrophin).

Function of TSH:

Acts on the Thyroid Gland: TSH stimulates the thyroid gland to produce thyroid hormones (T3 and T4), which regulate metabolism.

Regulation: The secretion of these hormones is regulated by the hypothalamus, which can either stimulate or inhibit their release depending on the body’s needs.

Question 10

Chromophobes
Secretory Granules: Chromophobes, which were once thought to be inactive, actually contain secretory granules.
Hormone Secretion: Chromophobe adenomas (tumors originating from chromophobes) often secrete hormones, particularly prolactin

Question 11

What are the Key Factors Influencing Hormone Secretion?

Answer 11

Neural Control:

Neural Stimuli: Signals from other parts of the brain (extrahypothalamic) can influence and sometimes override the usual control mechanisms of hormone secretion.

Impact of Stress and Mental Illness: Physical or emotional stress and mental disorders can affect hormone levels similarly to endocrine diseases.

Testing with Stress: Insulin-induced hypoglycemia is used to test anterior pituitary function by causing stress that stimulates hormone secretion.

ADH Secretion: Stress can also increase the secretion of ADH (antidiuretic hormone) from the posterior pituitary.

Feedback Control:

Negative Feedback Mechanism: The most common control mechanism, where increasing levels of target cell hormones suppress the secretion of trophic hormones.

Direct Suppression: High levels of target hormones can directly suppress the secretion of hypothalamic hormones.

Modification of Effect: Target hormones can also modify the effect of hypothalamic hormones on pituitary cells (long feedback loop).

Short Feedback Loop: Rising levels of pituitary hormones can suppress the secretion of hypothalamic hormones.

Inherent Rhythms

Pulses and Circadian Rhythms: Hypothalamic and pituitary hormones are released in intermittent pulses or follow a regular daily (circadian) rhythm.

Diagnostic Value: Disruptions in these rhythms can indicate endocrine disorders and can be useful in diagnosis.

Influence of Drugs

Neurotransmitter Action: Some drugs can stimulate or block the action of neurotransmitters like catecholamines, acetylcholine, and serotonin, affecting hormone secretion.

Examples:

Neuroleptic Drugs (e.g., Chlorpromazine and Haloperidol):

Interference with Dopamine: These drugs interfere with dopamine’s action.

Effects: This leads to reduced GH secretion (since dopamine normally stimulates GH release) and increased prolactin secretion (since dopamine normally inhibits prolactin).

Dopamine Agonists (e.g., Bromocriptine, Levodopa):

Dopamine-Like Action: Bromocriptine mimics dopamine, and levodopa is converted into dopamine in the body.

Effects: These drugs have the opposite effect of neuroleptics in normal subjects, reducing prolactin and increasing GH.

Acromegaly Treatment: Bromocriptine paradoxically suppresses excessive GH secretion in patients with acromegaly, although the exact reason is unknown.

Question 12

What are the Challenges in Interpretation/ measuring pituitary hormones?

Answer 12

Basal Hormone Assays: Measuring baseline levels of pituitary hormones in the blood can be challenging because:

Low Levels Aren’t Always Abnormal: Low hormone levels don’t necessarily indicate a problem.

Normal Levels Don’t Exclude Disease: Hormone levels within the normal range can still occur in individuals with pituitary disease.

Question 13

Diagnosing Hypopituitarism
Stimulation Tests: To diagnose suspected hypopituitarism (underactivity of the pituitary gland), direct measurement of pituitary hormones after stimulation is more reliable.
Examples of Stimulation Tests:
Administering a hormone that stimulates the pituitary and measuring its response.
Demonstrating the hyposecretion of target gland hormones after administering the relevant trophic hormone (hormones that stimulate other glands to produce hormones).
Secondary Failure: Prolonged hypopituitarism can cause secondary failure of the target gland, leading to diminished response even after stimulation

Question 14

Laboratory Tests
Presence or Absence: Lab tests can confirm whether hypopituitarism is present but cannot determine the cause.
Additional Diagnostics: Identifying the underlying cause requires other clinical methods such as radiological imaging.
Hypothalamus or Pituitary Dysfunction?
Differentiating Causes: It’s often difficult to distinguish between issues originating in the hypothalamus (which controls the pituitary) and those originating in the pituitary itself.
Isolated Hormone Deficiencies: More likely to stem from hypothalamic issues rather than pituitary problems.
Diabetes Insipidus: The coexistence of this condition (characterized by excessive thirst and urination due to ADH deficiency) suggests a hypothalamic disorder.
Biochemical Investigations

Evaluating Function:
Both Hypothalamic and Pituitary: Some tests evaluate the function of both the hypothalamus and the pituitary.

Pituitary Only: Other tests focus solely on pituitary function.
Differentiating the Site of Lesion: Some tests can help identify whether the issue is in the hypothalamus or the pituitary.

Question 15

Differentiation: Tests like TRH and GnRH stimulation can help distinguish between hypothalamic and pituitary dysfunction, although some distinctions are clearer than others.

Question 16

Example Tests
TSH Response to TRH:

TRH (Thyrotropin-Releasing Hormone) Test: This test can differentiate between hypothalamic and pituitary causes of secondary hypothyroidism.
Secondary Hypothyroidism: Characterized by low thyroid hormone levels due to a problem with the pituitary or hypothalamus.
GnRH Response in Hypogonadism:

GnRH (Gonadotropin-Releasing Hormone) Test: Used to differentiate causes of hypogonadism (underactive sex glands) due to gonadotropin deficiency.
Less Clear-Cut Differentiation: The response to GnRH may not always clearly indicate whether the problem is with the hypothalamus or the pituitary.

Question 17

How’s GH secreted?
It’s pulsatile secretion
It’s inhibition
It’s simulators

Answer 17

Control by GHRH:

GH-Releasing Hormone (GHRH): Produced by the hypothalamus and transported to the anterior pituitary via the hypothalamic portal system.

Somatotrophs: Cells in the anterior pituitary that release GH in response to GHRH.

Pulsatile Secretion

GH is released in pulses, typically 7-8 times a day, often associated with:

Exercise: Physical activity can trigger GH release.

Deep Sleep: GH secretion increases with the onset of deep sleep.

Post-Meal Glucose Drop: About an hour after eating, as blood glucose levels drop, GH is released.

Low Baseline Levels

At other times, GH levels in the blood are usually very low or undetectable, especially in children.

Inhibition of GH

Negative Feedback Pathway:

Somatostatin (GH-Release Inhibiting Hormone): Inhibits GH release and is produced not only in the hypothalamus but also in the gastrointestinal tract and pancreatic islet cells.

Insulin-Like Growth Factor 1 (IGF-1): Inhibits GHRH action, providing another layer of feedback control.

Stimulators of GH Secretion

Various factors can stimulate GH secretion, including:

Stress: Hypoglycemia (low blood sugar) is one form of stress that can increase GH levels.

Glucagon: A hormone that raises blood glucose levels.

Amino Acids: Certain amino acids, such as arginine, can stimulate GH release.

Drugs: Medications like levodopa (used in Parkinson’s disease) and clonidine (used for hypertension) can increase GH secretion.

Question 18

What are the Conditions Affecting GH Secretion?

Answer 18

Certain conditions can impair GH secretion, such as:

Obesity: Excess body weight can reduce GH levels.

Hypothyroidism: Low thyroid function can affect GH secretion.

Hypogonadism: Low sex hormone levels can impact GH.

Cushing’s Syndrome: Some cases of this condition can reduce GH levels.

High Steroid Doses: Use of large amounts of steroids can suppress GH secretion.

Question 19

What are the Various stimuli are used to assess GH secretory capacity, including:

Answer 19

Stress Induction: Such as inducing hypoglycemia.

Administering Glucagon, Arginine, or Specific Drugs: These can help evaluate GH response.

● some amino acids, for example arginine,

● drugs such as levodopa and clonidine.

Question 20

This means that the effects of Growth Hormone (GH) are largely carried out through the action of Insulin-like Growth Factors (IGFs

Question 21

IGF-1: One of the main types of IGFs, also known as Somatomedin C.
Plasma Concentrations of IGF-1 Correlate with GH Secretion:
The level of IGF-1 in the blood is directly related to the amount of GH being secreted. When GH levels are high, IGF-1 levels are also high, and vice versa.

Question 22

IGF-1 is responsible for carrying out many of the actions of GH. For example, it helps stimulate cell growth and development, particularly in ___&____

Answer 22

bones and muscles.

Question 23

What’s the Effects of GH on Metabolism

Answer 23

Carbohydrate Metabolism:

Antagonizes Insulin: GH opposes the insulin-mediated uptake of glucose by cells.

Glucose Intolerance: Excessive GH secretion can lead to glucose intolerance, similar to diabetes.

Fat Metabolism:

Stimulates Lipolysis: GH promotes the breakdown of fats, increasing the concentration of free fatty acids in the blood.

Free Fatty Acids and Insulin: Elevated free fatty acids can antagonize insulin release and action, contributing to insulin resistance.

Protein Metabolism:

Enhances Protein Synthesis: GH, along with insulin, stimulates the uptake of amino acids by cells, promoting protein synthesis.

Question 24

What Regulates the IGF-1 Production?

Answer 24

Nutritional Status:

Influence on IGF-1 Levels: Nutritional status is a key factor affecting IGF-1 production.

Undernutrition: Leads to low plasma IGF-1 concentrations, even though GH levels may be elevated. This suggests a feedback mechanism where low IGF-1 levels stimulate GH secretion.

Other Factors:

Adequate Nutrition and Thyroxine (T4): Both are essential for normal growth and IGF-1 production.

Puberty: The growth spurt during puberty is enhanced by androgens, which also play a role in increasing IGF-1 levels

Question 25

What are the potential causes of GJ hyper secretion?

Answer 25

Pituitary Adenomas:

Most cases of GH excess are due to acidophil adenomas of the anterior pituitary gland. These are benign tumors that cause the pituitary to produce too much GH.
Hypothalamic Stimulation: Sometimes, these adenomas are caused by excessive stimulation from the hypothalamus.
Malignant Tumors: Rarely, cancers can release GH or GH-releasing hormone (GHRH).
Multiple Endocrine Neoplasia (MEN):

Acromegaly can sometimes be part of a condition called multiple endocrine neoplasia, a genetic disorder that causes tumors in endocrine glands.

Question 26

What’s the clinical manifestation of GH hyper secretion?

Answer 26

Gigantism:

Before Epiphyseal Fusion:

Occurs when GH excess happens before the growth plates (epiphyses) of the bones fuse.

Results:

Abnormally tall stature, sometimes reaching heights of up to 2 meters.

The growth plates are responsible for lengthening bones during childhood and adolescence.

Hypogonadism:

Delayed puberty can accompany gigantism, delaying the fusion of the growth plates and contributing to excessive height.

Acromegaly:

After Epiphyseal Fusion:

Occurs when GH excess happens after the growth plates have fused in adulthood.

Results:

Enlarged bones of the hands, feet, and face, since long bones can no longer lengthen

Question 27

What are the possible complications of Acromegaly?

Answer 27

Health Complications:

Patients with acromegaly may suffer from various complications such as:

Infection: Due to a weakened immune system.

Cardiac Failure: Due to the strain on the heart from enlarged organs and tissues.

Pituitary Tumor Growth: Progressive growth of the pituitary tumor can cause further health issues

Question 28

What are the features of accromegaly?

Answer 28

Bone and Soft Tissue Enlargement:

Hands, Tongue, Jaw, Heart: Significant increase in size.

Facial Appearance: Noticeable changes due to jaw and sinus enlargement; gradual coarsening of features can go unnoticed for years.

Thyroid Gland: Enlargement may be detectable, but patients usually remain euthyroid (normal thyroid function).

Other Physical Features:

Excessive Hair Growth: Increased hair production.

Hyperhidrosis: Excessive sweating.

Sebaceous Gland Secretion: Increased oil production by skin glands.

Menstrual Disturbances:

Common in females with acromegaly.

Impaired Glucose Tolerance:

Present in about 25% of patients, with about half developing symptomatic diabetes mellitus.

Pancreas Response: Most patients’ pancreas secretes enough insulin to counteract GH’s antagonistic effect.

Question 29

Patients with accromegaly are predisposed to ?

Answer 29

Multiple Pre-Malignant Colon Polyposis: Increased risk of developing colon polyps.

Hypertension: Higher likelihood of high blood pressure.

Metabolic Abnormalities:

Hyperphosphataemia: Elevated phosphate levels in the blood.

Hypercalcaemia: Elevated calcium levels in the blood.

Hypertriglyceridaemia: Elevated triglyceride levels in the blood.

Pituitary Tumor Enchrochment

Question 30

What’s responsible for a the causes of accromegaly?

Answer 30

IGF-1 (Insulin-like Growth Factor 1):

Acts as a general growth factor and mediates many of GH’s effects, leading to the symptoms of acromegaly

Question 31

What are the Symptoms Due to Pituitary Tumor Encroachment?

Answer 31

Visual Field Defects:

Optic Chiasma Compression: May cause bitemporal hemianopsia (loss of peripheral vision on both sides).

Hormonal Deficiencies:

Progressive Destruction of Pituitary Gland: Can lead to deficiencies in other anterior pituitary hormones such as ACTH, LH, FSH, and TSH.

Raised Plasma Prolactin Levels: Due to the unique control mechanism of prolactin, which is inhibited by dopamine. Impairment of hypothalamic control leads to hyperprolactinaemia (high levels of prolactin).

Question 32

Unique Control Mechanism of Prolactin

Dopamine Inhibition:

Unlike most other pituitary hormones, prolactin secretion is primarily inhibited by dopamine.

Dopamine is a neurotransmitter produced by the hypothalamus.

When dopamine binds to receptors on lactotroph cells in the anterior pituitary gland, it suppresses prolactin release.

Impairment of Hypothalamic Control

Hypothalamic Control:

The hypothalamus regulates prolactin secretion by producing dopamine.

Normally, dopamine travels through the pituitary stalk to the anterior pituitary and binds to receptors on lactotroph cells, inhibiting prolactin release.

Impact of Tumors or Damage:

If a pituitary tumor grows large enough, it can compress or damage the pituitary stalk.

This compression can block the delivery of dopamine from the hypothalamus to the anterior pituitary.

Without sufficient dopamine inhibition, prolactin secretion from the anterior pituitary increases, leading to elevated levels of prolactin in the blood

Question 33

A patent comes to your hospital with accromegaly or gigantism how do you acces them?
Clinical features & biochemical test

Answer 33

Clinical Presentation

The diagnosis begins with observing the clinical features of GH excess:

In children, it can manifest as gigantism (excessive height).

In adults, it presents as acromegaly, characterized by enlarged hands, feet, facial features, and other symptoms discussed earlier.

Biochemical Tests

Plasma GH Concentrations:

Plasma GH levels are typically elevated in individuals with GH excess.

However, due to the natural episodic secretion of GH and its short half-life, random measurements can be misleading.

GH levels can fluctuate throughout the day, influenced by factors like sleep, stress, and meals.

Normal reference ranges are wide, making it difficult to distinguish between normal and moderately elevated levels based solely on random samples.

Glucose Suppression Test:

To confirm the diagnosis, a glucose suppression test is performed.

Normally, after consuming a 75-gram oral glucose load, plasma GH levels drop to very low levels (below 1 microgram per liter or 1 mg/L).

In patients with acromegaly, GH secretion is not suppressed by the glucose load. The GH levels either do not decrease significantly or might paradoxically increase.

This lack of suppression indicates autonomous GH secretion, which is characteristic of GH excess conditions.

Question 34

What are the signs of decreased GH in children & adults

Answer 34

Deficiency

In Adults

Symptoms:

Tiredness

Dyslipidemia (abnormal lipid levels in the blood)

Increased risk of cardiovascular disease

In Children

Short Stature:

GH deficiency can cause reduced growth rates, leading to short stature.

Affected children are often proportionally small, with normal birth weights but subnormal growth rates.

Question 35

Read Twice

Answer 35

Diagnosis:

Diagnosis of GH deficiency should only be made after excluding other causes of growth retardation and short stature.
Emotional deprivation can cause GH deficiency indistinguishable from organic causes by laboratory tests.
Specific conditions like Laron-type dwarfism (GH receptor defect) and Pygmy stature (GH receptor defect and low IGF-1 concentrations) must also be considered.

Question 36

Importance of Early Investigation
It is crucial to investigate children with reduced growth rates to identify those who might benefit from recombinant human GH replacement treatment.

Question 37

What are the causes of GH Deficiency

Answer 37

Idiopathic Deficiency of Hypothalamic GHRH:

The most common cause of isolated GH deficiency.

Often, other hormone secretions may also be impaired.

Organic Disorders:

Sometimes, GH deficiency results from organic disorders of the anterior pituitary gland or hypothalamus.

Inherited Forms:

Rare inherited forms of GH deficiency have been described.

Question 38

Idiopathic Deficiency of Hypothalamic GHRH
Definition:

“Idiopathic” means that the cause is unknown.
“GHRH” stands for Growth Hormone-Releasing Hormone, which is a hormone produced by the hypothalamus to stimulate the pituitary gland to release GH.
Details:

In many cases, the deficiency of GH in the body is due to a lack of GHRH from the hypothalamus.
This is the most common cause of isolated GH deficiency, meaning that only GH is deficient while other pituitary functions may be normal.
Additional Effects:

In some cases, the deficiency of GHRH might also affect the secretion of other hormones. The hypothalamus regulates several other pituitary hormones, so a problem in the hypothalamus can sometimes impact multiple hormones.
2. Organic Disorders
Definition:

“Organic” refers to physical or structural problems in the body.
Details:

GH deficiency can sometimes be due to a physical problem or damage to the anterior pituitary gland or the hypothalamus.
These problems can be due to:
Tumors in the pituitary or hypothalamus
Radiation therapy for brain tumors
Infections that affect the brain
Surgery that damages the pituitary or hypothalamus
Head injuries that affect these areas
Impact:

Such structural issues can impair the ability of the hypothalamus or pituitary gland to produce and secrete GH.
3. Inherited Forms
Definition:

These are genetic forms of GH deficiency passed down through families.
Details:

Rare inherited forms of GH deficiency occur due to mutations in genes that are crucial for the production or function of GH or its receptors.
Examples include:
Laron Syndrome: A condition where there is a mutation in the GH receptor, so the body produces GH, but the tissues cannot respond to it properly.
Pygmy Stature: Characterized by a defect in the GH receptor and low levels of IGF-1 (Insulin-like Growth Factor 1), which is crucial for growth and development.

Question 39

How to approach/ diagnosis GH deficiency

Clinical History: Assess birthweight, intrauterine growth, and calculate target height.

Exclusions: Rule out other conditions affecting growth.

Examination: Evaluate for syndromes, measure bone age, and growth velocity.

Hormone Priming: For children with advanced bone age.

Biochemical Tests: Plasma IGF-1 and urinary GH excretion as initial screening, with follow-up blood tests at specific times.

Adequate Response: GH level > 20 mU/L after specific stimuli indicates normal GH secretion.

4o

Answer 39

Birthweight and Intrauterine Growth:

Check if the child had normal birthweight or experienced intrauterine growth retardation.

Mid-Parental Height:

Calculate target height to assess normal growth potential.

Formula for boys: (Father′sheight+Mother′sheight)/2+6.5cm(Father’s height + Mother’s height) / 2 + 6.5 cm(Father′sheight+Mother′sheight)/2+6.5cm

Formula for girls: (Father′sheight+Mother′sheight)/2−6.5cm(Father’s height + Mother’s height) / 2 - 6.5 cm(Father′sheight+Mother′sheight)/2−6.5cm

Normal Growth Rate:

More than 5 cm per year in mid-childhood is considered normal.

Exclusion of Other Conditions:

Ensure that conditions like hypothyroidism, chronic diseases, malabsorption, poor nutrition, and failure to thrive are not the cause of growth issues.

Clinical Examination:

Look for syndromes, assess pubertal status, measure bone age, and evaluate growth velocity using Tanner–Whitehouse charts.

Check proportionality of limbs.

Karyotyping: May be necessary if a chromosomal disorder like Turner’s syndrome (45,X0) is suspected.

Physiological Reduction in GH Secretion

At the end of pre-puberty, GH secretion naturally reduces.

In children with bone age over 10 years, priming with sex hormones (ethinyloestradiol for girls and testosterone for boys) before testing can be necessary to stimulate GH secretion.

Biochemical Investigations

Challenges:

GH secretion is episodic.

GH assays vary between laboratories.

GH response to provocative stimuli is variable.

Basal plasma GH concentrations in normal children are often low.

Screening Tests:

Plasma IGF-1 Concentration: A low level can indicate GH deficiency.

Urinary GH Excretion: 24-hour collections or timed overnight collections can be a safe screening method.

Timing of Blood Tests:

Perform blood tests when physiologically high GH concentrations are expected (60–90 minutes after the onset of sleep or 20 minutes after vigorous exercise).

An adequate GH response is indicated by an absolute level greater than 20 mU/L (7 µg/L), making GH deficiency unlikely.

Note: GH cut-offs may be age and assay dependent

Question 40

What are the Disorders of Posterior Pituitary Hormone Secretion

Answer 40

Posterior Pituitary Disorders:

Rare compared to anterior pituitary disorders.

Diabetes Insipidus (DI):

Caused by deficiency of antidiuretic hormone (ADH).

Presents as polyuria (excessive urine production).

Syndrome of Inappropriate ADH Secretion (SIADH):

Results in hyponatremia (low blood sodium) due to water retention.

Question 41

Functional Reserve of the Anterior Pituitary Gland
Functional Reserve:

The anterior pituitary gland has a built-in “functional reserve.” This means it has the capacity to continue functioning normally even when a portion of it is damaged or not working properly.
Because of this reserve, the gland can compensate for some degree of damage or dysfunction without showing any noticeable symptoms.
Threshold for Clinical Symptoms:

Clinical symptoms of pituitary hormone deficiency generally do not become apparent until a substantial portion of the gland (about 70%) is destroyed or non-functional.
In other words, as long as less than 30% of the gland is affected, the remaining healthy tissue can often produce enough hormones to meet the body’s needs.

Question 42

What are the types & causes of hypo pituitarism

Answer 42

Panhypopituitarism:
Involves deficiencies in all pituitary hormones.
Partial Hypopituitarism:
Involves deficiencies in one or more, but not all, pituitary hormones.
Causes of Hypopituitarism:

Tumors of the pituitary or surrounding brain areas.

Infections, inflammation, or injuries affecting the pituitary.

Genetic mutations or developmental abnormalities.

Question 43

What are the clinical features of hypo pituitarism

Answer 43

Clinical Features:

Often first detected by signs of:

Pituitary or brain tumors (clinical and radiological evidence).

Hypogonadism (low sex hormone levels).

Adrenocortical insufficiency (low cortisol levels).

Short stature in children (due to GH deficiency).

Hypothyroidism (low thyroid hormone levels).

Question 44

What are the Consequences of pituitary hormone deficiencies

Answer 44

Secondary Hypogonadism (Gonadotrophin Deficiency)

Caused by Deficiency of Gonadotrophins: Gonadotrophins are hormones (LH and FSH) that stimulate the gonads (ovaries in women and testes in men). When the pituitary gland doesn’t produce enough gonadotrophins, it leads to secondary hypogonadism.

In Women:

Amenorrhea: This is the absence of menstrual periods because the ovaries are not stimulated properly.

Infertility: Difficulty in conceiving due to lack of ovulation.

Atrophy of Secondary Sexual Characteristics: There is a loss of features like breast development and body hair because the hormones responsible for these characteristics are lacking.

In Men:

Loss of Axillary and Pubic Hair: Reduction in body hair due to decreased testosterone.

Impotence or Loss of Libido: Erectile dysfunction and decreased sexual desire due to low testosterone levels.

In Children:

Delayed Puberty: Puberty is late or doesn’t occur because the hormones needed to trigger these changes are insufficient.

Secondary Adrenocortical Hypofunction (ACTH Deficiency)

Caused by Deficiency of Adrenocorticotropic Hormone (ACTH): ACTH stimulates the adrenal glands to produce cortisol. When ACTH levels are low, cortisol production is affected.

Contrast with Addison’s Disease:

No Hyperpigmentation: In Addison’s disease (primary adrenal insufficiency), there is hyperpigmentation because ACTH levels are high, trying to stimulate the failing adrenal glands. In secondary adrenocortical hypofunction, ACTH levels are low, so this symptom is not present.

Aldosterone Secretion Remains Normal: Aldosterone, which controls sodium and water balance, is regulated by the renin-angiotensin system and not by ACTH. Hence, sodium and water retention issues and hyperkalemia (high potassium) typical of Addison’s disease do not occur.

Cortisol Deficiency:

Hyponatremia: Low sodium levels due to the body’s inability to excrete water properly.

Hypotension: Low blood pressure because cortisol helps maintain vascular tone.

Increased Insulin Sensitivity: This can lead to low blood sugar (hypoglycemia) during fasting as cortisol helps regulate blood sugar levels.

Secondary Hypothyroidism (TSH Deficiency)

Caused by Deficiency of Thyroid-Stimulating Hormone (TSH): TSH stimulates the thyroid gland to produce thyroid hormones. When TSH levels are low, thyroid hormone production is affected.

Symptoms Similar to Primary Hypothyroidism:

Fatigue: Feeling tired all the time.

Weight Gain: Gaining weight without changes in diet or activity.

Cold Intolerance: Feeling unusually cold in a normal environment.

Prolactin Deficiency

Prolactin is responsible for milk production after childbirth.

Failure to Lactate:

Sheehan’s Syndrome: This condition can occur after severe blood loss during childbirth, leading to pituitary infarction (death of pituitary tissue), resulting in an inability to produce milk.

Tumor-Related Hyperprolactinemia:

When a pituitary tumor compresses the pituitary stalk, it can impair the inhibition of prolactin by dopamine, leading to increased prolactin levels.

Galactorrhea: Abnormal lactation not associated with childbirth due to elevated prolactin levels.

Growth Retardation in Children:

Growth Hormone (GH) Deficiency:

Leads to slower growth and shorter stature in children.

Thyroid-Stimulating Hormone (TSH) Deficiency:

Results in lower thyroid hormone levels, contributing to growth retardation.

Question 45

Progressive Pituitary Damage and Hormone Deficiencies
1. General Progression:

When the pituitary gland is progressively damaged, it typically first shows deficiencies in _____&_____

Deficiencies in _____&_____ can occur much later.

Answer 45

gonadotrophins (hormones that stimulate the gonads) and growth hormone (GH).

adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone (TSH)