Hypocortisolism and emerging endocrine diseases

  • Hypocortisolism
  • Emerging endocrine disorders: thyroid cancer

 

ADRENAL

This is a particularly important issue as acute crises may occur during stress periods in undiagnosed patients. Several studies reported a significant prevalence of “biochemical” central adrenal insufficiency (CAI), ranging from 15% to 45.8 %, in children, adolescent and adults with TM. The diagnosis of AI is relatively simple when glucocorticoid secretion is profoundly depressed. However, AI can present a difficult diagnostic challenge, especially when adrenal insufficiency is partial. 
Clinical adrenal insufficiency (AI) and adrenal crisis are very rare. On the other hand subclinical impairment of adrenocortical function in patients with thalassaemia is not uncommon; but of little or no clinical impact under basal conditions and may have a potential relevance during stressful events. 

Livello di adrenalina nel paziente adulto

The pathophysiological basis of “biochemical” AI inTM has not yet been well-defined. Chronic transfusions induce iron overload in several
organs, including adrenal and pituitary glands.Therefore, it is possible that pituitary iron depositionmight reduce ACTH secretion leading to CAI , andthe adrenal glands might also be directly affected byiron toxicity.
 Adrenalin iron overload

There are two methods to differentiate betweenprimary and secondary AI. First is done bymeasuring plasma ACTH concentration in the basalfasting AM blood sample. If it is higher than normal,the patient has primary AI, whereas if it is low, thediagnosis of secondary or tertiary AI should beconsidered.
The second method assesses the serum cortisolvalues in response to exogenous corticotropin(ACTH) stimulation or insulin tolerance test (ITT).

The agent most commonly used is synthetic ACTH (1-24) (cosyntropin), which has the full biologic potency of native ACTH.
The text is useful for the diagnosis of AI but not for the differential diagnosis between peripheral and central forms.


Signs and Symptoms

Patients are usually asymptomatic. Clinical adrenal insufficiency and adrenal crisis are very rare.
Adrenal androgen levels might be decreased explaining the poor development of pubic and axillary hair observed in thalassemic adolescents (Figure).

Risposta ad ACTH test dai pazienti talassemici


Investigations


1. Fasting Cortisol level is screened yearly, especially in growth hormone deficient patients during rhGH therapy.
2. If low (Figure) do ACTH stimulation test.
3. Patients with abnormal screening are referred to endocrinology for further evaluation.
4. Cosyntropin: 1 μg intravenously is given and cortisol levels are measured at 30 and 60 minutes after dosing.
5. Peak total cortisol level 18 μg/dl or greater isusually considered normal.


Valutazione della funzionalità surrenalica 

Legend: ITT (insulin Tolerance Test)


Recommendation 

Thalassaemia patients more than 10 years of age, especially those with wasting and other endocrinopathies should be monitored annually for hypoadrenalism. 


Treatment 

Subclinical impairment of adrenocortical function in patients with thalassaemia is of little or no clinical impact under basal conditions but may have a potential relevance during stressful events. Accordingly, glucocorticoid treatment coverage might be advised for stressful conditions.

Emerging endocrine disorders in thalassemia:
Thyroid cancer 

Thyroid cancer is the most frequent endocrine neoplasm in the general population. Its incidence is 5-10/100,000 per year, with an annual death rate of 0.2-1.2/100,000 in men and 0.4-2.8/100,000 in women. In thalassaemia patients the frequency of this disease is unknown.
Thyroid nodules were found in 8.6% of 58 examined thalassaemia major or intermedia patients.
The occurrence of malignancies in thalassaemic patients is an emerging concern for physicians.

In the last 10 years, in a single Thalassaemia Unit following 195 thalassaemic patients, eleven cases of carcinoma were diagnosed: 4 cases of liver, 1 of lung,1 of adrenal gland and 5 cases of papillary thyroidcarcinoma (patient mean age 42.6 years; Figure). 

A diagnosis of incidental papillary thyroid microcarcinoma (PTMC) was made in 3 female patients with iron overload. According to the World Health Organization, PTMC is defined as papillary thyroid carcinoma measuring < or = 10 mm in the greatest dimension. Two patients were HCV positive.Il ruolo del ferro 


Investigations

A thyroid ultrasonography is recommended for all adult thalassaemic patients in addition to the annual FT4 and TSH assessment.To exclude thyroid malignancy, fine needle biopsy (FNAC) under US guidance and histological confirmation must be required.

US of thyroid nodule

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Treatment

Surgical treatment is particularly recommended for those patients with nodules that are considered cancerous. This is primarily detectable by FNAB. Even though FNAB diagnosis may not indicate a strictly cancerous diagnosis, it may indicate a diagnosis that is sufficiently suggestive of cancer to warrant surgical treatment.Thyroid nodules that are benign by FNA or too small to biopsy should still be watched closely with ultrasound examination every 6 to 12 months and annual physical examination by your doctor.Surgery may still be recommended even for a nodule that is benign by FNA if it continues to grow, or develops worrisome features on ultrasound over the course of follow up.