Disordini delle ghiandole surrenali: anatomia, fisiologia e patologie

Medicina Interna

Disordini delle ghiandole surrenali

Anatomia e fisiologia delle ghiandole surrenali

Prof. Paolisso

1. Adrenal glands anatomy and physiology

• The adrenal glands (also known as suprarenal glands) are endocrine glands divided in:
  • Adrenal cortex (outer part) ->production of mineralocorticoids (glomerular part), glucocorticoids (fascicular part), and androgens (reticular part).
  • Adrenal medulla (inner part)-> production by chromaffin cells of catecholamines (adrenaline and noradrenaline). Approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine) are secreted here.
• Glucocorticoids are responsible for numerous functions:
  • increase in 1 energy substrates with increased 1 gluconeogenesis and hepatic 1 glycogenolysis,
  • increased 1 proteolysis with renal nitrogen excretion,
  • increased 1 peripheral lipolysis and ™ lipogenesis in central sites,
  • inhibition of the immune response.
• The production of glucocorticoids is regulated by ACTH, which is derived from pro- opiomelanocortin and whose release is in turn controlled by CRH, plasma free cortisol concentration, stress and the sleep-wake cycle.
• Androgen production is also regulated by ACTH.
• The secretion of mineralocorticoids, on the other hand, is regulated by the renin angiotensin-aldosterone system (RAAS), which is mainly dependent on the volemia, plasma osmolarity, activation by the sympathetic nervous system. In the kidneys, in the juxtaglomerular system, the juxtaglomerular cells (baroreceptors), assisted by the macula densa (chemoreceptors) are responsible for the production of renin, which converts the angiotensinogen produced in the liver into angiotensin 1, which is then converted into angiotensin 2 in the pulmonary vascular bed, thanks to the action of the of the ACE enzyme. Ang2 causes the release of aldosterone and has a series of of other functions: it causes peripheral vasoconstriction, increases the secretion of ADH and the reabsorption of sodium and water in the kidneys with consequent increase in plasma volume, stimulates the sensation of thirst at the central level, increases cardiac function and remodeling.
• In reality, ACTH also carries out its activity upstream of hormonal production, indeed it activates at the level of the adrenal cortex the synthesis of pregnenolone, which is the precursor of glucocorticoids (cortisol), mineralocorticoids (corticosterone, from which aldosterone derives) and sex hormones (dehydroepiandrosterone)Internal Medicine - Paolisso - Endocrinology and metabolism disorders

Insufficienza surrenalica

Eziologia dell'insufficienza surrenalica

1. ADRENAL INSUFFICIENCY

Adrenal glands produce hormones necessary for normal body functioning; the deficiency of these hormones is called adrenal insufficiency.

1.1 Etiology

• Primary (Addison's disease)
  • Autoimmune (idiopathic adrenal atrophy)
    • The most frequent.
    • The adrenal cortex is selectively destroyed, probably by cytotoxic T lymphocytes, involving its 3 zones (firstly the glomerular - at the beginning there is an increase in plasma renin activity with normal or low aldosterone levels - after the fascicular and lastly the reticulate).
    • Clinical signs are manicured when 90% of > gland is destroyed.
    • It can be related to other autoimmune diseases (DM type 1, vitiligo, autoimmune thyroid disease, etc.) and is sometimes part of an autoimmune polyglandular syndrome (SPA).
    • 50-70% of patients have antibodies against adrenal steroidogenesis enzymes (21-hydroxylase, etc.).
  • Tuberculosis
    • Both the cortical and medullary are destroyed, which in the past was the most frequent. In tuberculous adrenalitis, the adrenal gland is initially hypertrophied, then fibrosis occurs and may remain normal in size or become atrophic, with the presence of calcifications in 50% of cases.
  • Infrequent Causes
    • Bilateral hemorrhage (due to meningococcal sepsis or Waterhouse- Friderichsen syndrome, coagulopathies or anticoagulant therapy),
    • bilateral infarction,
    • fungal or viral infections (CMV, HIV, etc.),
    • infiltration (metastases, amyloidosis, sarcoidosis, hemochromatosis),
    • Neoplastic diseases-> Question: which is the main cancer leading to adrenal glands metastasis? LUNG cancer, which is very often diagnosed because patients present adrenal problems.
    • surgical adrenalectomy,
    • drugs (mitotan, methyrapone, , ketoconazole, aminoglutethimide).
    • Genetic (adrenoleukodystrophy)Internal Medicine - Paolisso - Endocrinology and metabolism disorders
• Secondary
  • Adrenal insufficiency linked to pituitary alterations, so. concerning the secretion of ACTH.
  • This condition can occur in isolation or in the context of multiple hypopituitarism deficits, ranging from hypopituitarism to panhypopituitarism.
  • In this case, adrenal insufficiency is secondary to an ACTH deficiency and therefore to a lack of ACTH stimulus on the fasicular and reticular area of the adrenal gland. On the other hand, the functionality of the glomerular zone remains intact because it is regulated by the renin, angiotensin, aldosterone axis and not by ACTH.
• Tertiary
  • Adrenal insufficiency linked to hypothalamic alterations, with reduced V release of CRH and therefore less stimulation on the pituitary gland to the release of ACTH and Vaxial stimulus on the release of cortisol by the adrenal gland.
  • In these two cases, only the fasciculate (glucocorticoid production) and reticular (androgens production) zones are affected while the secretion of mineralocorticoids remains intact.

Adrenal insufficiency

Primary

Secondary

+

Infectious adrenalitis (e.g., tuberculosis)

Bilateral adrenal infarction/ hemorrhage

Pituitary abnormality

Autoimmune adrenalitis

Bilateral or pharmacologic adrenalectomy

Congenital ACTH deficiency

Hypothalamic abnormality

Adrenal infiltration (e.g., metastasis, sarcoidosis)

Sintomi e segni clinici dell'insufficienza surrenalica

2.2.Clinical symptoms and signs

• weakness and fatigue
• lack of appetite
• nausea, vomiting
• needs to eat salt.
• muscle aches, joint, abdominal
• dizziness
• depression
• weight loss
• hypotension
• pigmentation of the skin (mucous membranes, palms) -> particularly in primary
• loss of axillary and pubic hair.

Bronze Pigmentation of Skin

Hypoglycemia

Changes In Distribution of Body Hair

Postural Hypotension

Gl Disturbances - Weight Loss Weakness

Adrenal Crisis: Profound Fatigue Dehydration Vascular Collapse (+BP) Renal Shut Down #Serum NA 1Serum K THIRUER TFG 02007 Nursing Educat

Adrenal crisis-> profound fatigue, dehydration, vascular collapse (\ BP), renal shut down, serum Na, 1 serum potassium-> it could be associated with bradyarrhythmias. (Hypokalemia can lead to tachyarrhythmias).Internal Medicine - Paolisso - Endocrinology and metabolism disorders

Aspetti clinici della malattia di Addison

1.3 Addison disease: Clinical aspects

From a pathophysiological point of view in Addison's disease we have both: mineralocorticoids (aldosterone) and glucocorticoids (cortisol) are deficient.

• Because mineralocorticoids stimulate Na reabsorption and K excretion deficiency results in -> increased 1 excretion of Na and excretion of K+, mainly in urine but also in sweat, saliva, and the gastrointestinal tract. A low serum concentration of sodium (hyponatremia) and a high concentration of potassium (hyperkalemia result.
• Urinary salt and water loss cause severe dehydration, plasma hypertonicity, acidosis, decreased circulatory volume, hypotension, and, eventually, circulatory collapse. However, when adrenal insufficiency is caused by inadequate adrenocorticotropic hormone (ACTH) production (secondary adrenal insufficiency), electrolyte levels are often normal or only mildly deranged, and the circulatory problems are less severe.
• Glucocorticoid deficiency contributes to hypotension and causes severe insulin sensitivity and disturbances in carbohydrate, fat, and protein metabolism. In the absence of cortisol, insufficient carbohydrate is formed from protein; hypoglycemia and decreased \ liver glycogen result. Weakness follows, due in part to deficient neuromuscular function. Resistance to infection, trauma, and other stress is decreased. Myocardial weakness and dehydration reduce cardiac output, and circulatory failure can occur.
• A decreased blood cortisol level results in increased pituitary ACTH production and increased blood beta-lipotropin level. Beta-lipotropin has melanocyte- stimulating activity and, together with ACTH, causes the hyperpigmentation of skin and mucous membranes characteristic of Addison disease. Thus, adrenal insufficiency secondary to pituitary failure does not cause hyperpigmentation.

So, the symptoms and signs can be explained by: (morbo di Addison)

• mineralcorticoid deficiency-> electrolyte imbalance: hyponatremia, hyperkalemia, arterial hypotension (orthostatic);
• glucocorticoid deficiency-> hypoglycemia, anemia, eosinophilia, lymphocytosis, asthenia, adinamy, anorexia, nausea, vomiting, weight loss.

In secondary and tertiary adrenal insufficiency: lack of signs and symptoms of mineralcorticoid deficiency (WHITE ADDISON).

Diagnosi di laboratorio dell'insufficienza surrenalica

1.4 Laboratory

• Hyponatremia and tendency to hypoglycemia-> They are present in primary and secondary adrenal insufficiency.Internal Medicine - Paolisso - Endocrinology and metabolism disorders
• Hyperkalemia, hypochloremia and metabolic acidosis-> They occur only in primary adrenal insufficiency.
• Normocitic anemia, lymphocytosis, eosinophilia, neutropenia.

Diagnosi della malattia di Addison

1.5 Diagnosis

The diagnosis of Addison's disease is done by looking:

• subnormal levels of serum cortisol
• levels fail to rise over basal levels with ACTH stimulation test (Latter indicates primary adrenal disease; positive response to ACTH stimulation indicates functioning adrenal gland).
• Abnormal lab findings:
  • hyperkalemia, hypochloremia, hyponatremia, hypoglycemia
  • anemia, 1 BUN (because of increased protein breakdown), low urine cortisol levels (urinary 17- OHCS and 17 KS);

Sospetto di insufficienza surrenale

Test all'ACTH

1. Prelevare cortisolo basale 2. Somministrare ACTH 3. Prelevare cortisolo dopo 30 minuti (stimolato)

Valutare cortisolo basale

<3 µg/dl 3-18 µg/dl >18 µg/dl

Conferma ISR

Valutare cortisolo stimolato

Esclude ISR

<18 µg/dl >18 µg/dl

Conferma ISR

Esclude ISR primaria

Possibile ISR secondaria (valutare test ipoglicemia in caso si sospetti elevato)

Figura 4.10: Diagnosi d'insufficienza surrenalica (ISR).

• ECG-> voltage, vertical QRS axis, peaked T waves from hyperkalaemia ("a tenda"), with tendency to bradycardia;
• CT and MRI used to localize tumors and identify adrenal calcifications or enlargement; The adrenal glands and pancreas are more easily seen with MRI. We prefer in this case the MRI because CT scan does not allow you to have a view of the posterior parts of the brain, while MRI "covers" all the brain parts. So any lesion in the posterior part of the brain is lost by making a CT scan. Of course, MRI takes more time to be done and if a faster diagnosis is needed and CT is appropriate for the parts of the body under investigation, it can also be done. Sometimes in order to make the point faster, CT scan is firstly done and later there can be a deeper investigation making also an MRI. Question: focusing more on the two techniques: in general, when do you ask for a CT scan and when for a MRI? Answer: CT scan is used for hard tissues, like bone tissue (obviously in ER you have no time to use the contrast medium); MRI is used for soft tissues. The adrenal glands and pancreas are more easily seen with MRI. Question: in which other cases you are obliged to use CT scan instead of MRI? Answer: pacemakers (usually the oldest ones).