Effects of Noradrenaline
- Increases B.P.
- Decreases heart rate
- Minimal increase in gut movement
- Minimal dilation of airways
- Dilation of pupils
Other hormones like leu-enkephalin and met enkephalin are also produced but their function is not clear.
Clinical Abnormalities
Primary Hyperaldosteronism
It is observed in 2% of patient suffering from hypertension. Most common cause of this hormonal disorder is
an aldosterone-producing adenoma also known as Conn's syndrome. While, other causes includes idiopathic
hyperaldosteronism, primary adrenal hyperplasia, dexamethasone suppressible hyperaldosteronism and adrenal
cortical carcinoma.
Primary hyperaldosteronism can be distinguished from other causes of hyperaldosteronism by high levels of
plasma aldosterone (PA) and low plasma renin activity (PRA). As in secondary hyperaldosteronism, high PRA
and PA is observed, whereas, low PRA and PA is observed in patients with real or apparent mineralocorticoid
excess which is not caused by aldosterone.
Diagnosis
For screening, PA:PRA ratio is used, and screening procedure is performed ideally when the patient is not taking
any medications for 2 to 4 hours before testing, along with 2 hours of standing. Once primary hyperaldosteronism
is suspected based on the PA:PRA ratio then confirmatory testing is performed, wherein, 2 liters of saline for over
4 hours is given to the individual to check possible aldosterone suppression (saline suppression test) or 24 hr
urinary aldosterone test is done.
Adrenal Insufficiency (AI)
Al also known as hypocortisolism is a condition in which either, adrenal gland produces insufficient amount of
cortisol (primary Al) or, there is a lack of CRH or corticotropin secondary or tertiary Al). In primary Al called Addison's
disease, there is cortisol or aldosterone deficiency and in secondary or tertiary Al, Adrenal glands can synthesize
aldosterone but, not cortisol.
Autoimmune diseases, adrenal hemorrhage, HIV, infiltration of the adrenals by Tuberculosis, sarcoidosis or
amyloidosis can cause primary Al; and infiltration of anterior pituitary, hypothalamus by craniopharyngioma,
pituitary adenoma, metastasis, sarcoidosis, tuberculosis or suppression of corticotropin by steroid use can
cause secondary or tertiary Al.
Weakness, fatigue, anorexia, nausea, abdominal pain and diarrhea are the manifestations of chronic Al.
Hyponatremia can be seen with all the form of Al but, hyperkalemia is seen only in primary Al due to lack of
aldosterone. In acute Al, decreased cardiac output and relative hypovolemia can be observed. If, Al is left
untreated, it can lead to coma and even death.
Diagnosis
Diagnosis of Al involves measurement of serum cortisol preferably in moming or corticotropin-stimulation test.
For corticotropin-stimulation test, synthetic cosyntropin is given intravenously to measure the cortisol level at
baseline, at 30 minutes and at 60 minutes. Several other methods are also developed for measuring serum free
cortisol but, they are technically demanding and expensive.
Cushing's Syndrome
This syndrome is caused due to persistent and inappropriate excess of cortisol caused due to excess glucocorticoids
production by adrenal glands, excess corticotropin (CRH) production or exogenous glucocorticoids. Excess production
by adrenal glands is observed due to adrenal adenoma, carcinoma or nodular hyperplasia. Likewise, corticotropin
can be produced by anterior pituitary gland or by paraneoplastic syndrome like bronchial carcinoid or lung cancer.
Also, ectopic production of CRH can be produced by bronchiali
carcinoid, medullary thyroid cancer or metastatic prostate cancer.
Hypertension, Diabetes mellitus, irregular menses, weight gain, androgen-type hirsutism, ecchymoses, myopathy,
osteopenia, truncal obesity, neuropsychological disturbances and purple striae are all the clinical manifestations
of Cushing's Syndrome.
Diagnosis
Initially, screening tests are done for diagnostic evaluation of this abnormality. Among others, the major difficulty
observed in screening process is high falsepositive rates. Initial screening test like 24 hrs urinary measurement
of free cortisol (95-100% sensitive and 98% specific) are done. Alternately, test like 1-mg overnight dexamethasone
suppression is often done for screening Cushing's Syndrome. A newer technique was made available for
evaluating Cushing's Syndrome which involves measurement of salivary cortisol levels.
Congenital Adrenal Hyperplasia (CAH)
It is a group of inherited diseases which affects the levels of steroid hormones produced by adrenal cortex.
CAH results in defective activity of one of five enzymes in the adrenal cortex causing decreased production
of corticotropin, excess production of hormones proximal to the defective enzyme and glandular enlargement.
21-hydroxylase deficiency (defect in the P450c21enzyme) and 11-3-hydroxylase deficiency (defect in the
P450c11 enzyme) are the two most common types of CAH. With 90% of cases causing by 21 hydroxylase deficiency,
it is further classified into classic and non classic forms.
Salt-wasting and simple virilizing agents constitutes the classic forms of 21-hydroxylase deficiency CAH. In
saltwasting 21-hydroxylase deficiency CAH, girls and boys may have Addisonian crisis and hypotension along
with ambiguous genitalia in girls since birth. While, in simple virilizing 21-hydroxylase CAH, girls have ambiguous
genitalia but do not experience Addisonian crisis. The non classic form of 21-hydroxylase deficiency is more common
than the classic form.
Diagnosis
21-hydroxylase deficiency increases the hormone 17 Oh Progesterone along with excess testosterone and
DHEA-S helping in its diagnosis by looking for an increase in 17-hydroxyprogesterone from baseline to 60
minutes during a corticotropin-stimulation test.
Adrenal Tumor
Uncontrolled growth in the healthy cells can leads to the formation of a tumor. It can either be benign or
malignant. Further, these tumors can be functional (secreting excessive hormones) or non functional.
Among many, Adenomas are the most common form of adrenal gland tumor. Most of them are non functional
while some are functioning with majority of them secreting cortisol. It is also called adrenocorticol adenoma.
Adrenocortical carcinoma is rare and can be functional or non functional. If it is functional, it may produce
more than one hormones. Its location is deep in the retroperitoneum making it difficult for detection until
they become large.
Incidentalomas are the term used to refer all those tumors found unexpectedly during diagnosis of some
other conditions requiring PET-CT Scan or MRI scans of the abdomen. Most of these are benign but some can be
malignant or functioning and needs to get removed.
Among others, pheochromocytoma, myelolipomas, paragangliomas, aldosteronomas and others are all
capable of affecting adrenal gland or its functions.
Diagnosis
Several biochemical tests are done in order to determine the type of adrenal tumors especially if it is functioning
or non functioning. These test helps in determining catecholamines, ACTH, DHEAS, aldosterone, vanillylmandelic
acid levels along with assessing creatinine, plasma renin activity and others. Additionally, imaging techniques like
computed tomography (CT) or magnetic resonance imaging (MRI) can also be done for evaluating adrenal lesions
with primary goal of distinguishing benign from malignant.
Pheochromocytoma
These are paraganglionic chromaffin cell tumors which are relatively uncommon. Pheochromocytoma are found in
the adrenal medulla and the extra-adrenal paraganglia cells. Microscopic studies reveal whirls or sheets like
arrangement of these tumor cells having granular basophilic or eosinophilic cytoplasm with nuclear pleomorphism.
It is capable of producing, storing and secreting catecholamines. In some cases, it also secretes dopamine,
Vasoactive intestinal peptide (VIP), Bendorphines and variety of other substances which can complicate the
clinical manifestations.
Its symptoms are non-specific and are similar to other conditions, ultimately, referred as 'great mimic' by the
professionals. Headache, hypertension, palpitations, tachycardia, anxiety, nausea are the few clinical features
among others.
Diagnosis
Several biochemical tests like plasma catecholamines, and 24 hrs urine for catecholamines, noremetanephrines
and metanephrines are required for confirming the diagnosis. Once the clinical evidences are compelling about
its presence then only tumor localization by different imaging techniques should be considered, Techniques like
computed tomography (CT) or magnetic resonance imaging (MRI) are the recommended ones.
Adrenal Fatigue-Is it real?
it is often used by some doctors and healthcare practitioners to describe 'overuse' of adrenal glands due to
chronic stress; eventually resulting in functional failure of adrenal glands. According to a review on adrenal
fatigue, there were 6,40,000 results showing on Google when the term 'adrenal fatigue' was searched, despite
this, endocrinology societies has not recognized it due to the lack of evidences for its existence.
Conversely, some medical societies claims that adrenal fatigue is real. Additionally, certain tests like estimation
of serum basal cortisol levels and salivary cortisol rhythms have been ordered for the patients suspected of this
condition by some practitioners. And, if patient is found to have impaired results then they are treated with
corticosteroids regardless of its cause.
The use of corticosteroid for the treatment of adrenal fatigue leads to considerable debate among medical
professionals. Some stated the fact that use of corticosteroids showed significant improvement in patients.
Others claim that several adrenal fatigue sufferer never received the adequate treatment due to strict diagnostic
criteria set by endocrinologists for prescribing corticosteroids. In contrast to this, counterarguments were
more focused on the risks involved in the use of corticosteroids. As, even in low doses, these steroids increases
the risks of osteoporosis, myopathy, cardiovascular disease, psychiatric disorders and others.
Several theories on how adrenal failure could be the genesis for fatigue may be tempting for some along with its
widespread use of the term but, the studies completely focused on this subject still remains few, that too only
descriptive. Therefore, several questions still lingers to the mind of a fervid reader, questions like; Adrenal fatigue
is actually a condition or not? Does it cause adrenal failure? What could be the useful Diagnostic Test for this
conditions? And above all, whether 'Adrenal Fatigue' is real or not?
