Fine needle aspiration cytology of thyroid nodules

According to National Guidelines for the management of thyroid cancer published in March, 2002, fine needle aspiration cytology (FNAC) should be performed in planning for surgery in patients with suspected thyroid lesions.

Ultrasound guidance may be of value in aiding FNAC but is not mandatory. A surgeon or physician with reasonable expertise may do it without assistance from ultrasound guidance.

Non-diagnostic histology results should lead to repeat FNAC. Two diagnostically benign cytology results from the lesion at least 3 to 6 months apart are deemed adequate to exclude malignancy. Suspicious cytology should be taken seriously and the patient referred for excision, as in the case of malignant cytology from FNAC.

Reference

• http://www.british-thyroid-association.org/guidelines.htm

Maturity Onset Diabetes of the Young (MODY)

Features of Maturity Onset Diabetes of the Young (MODY) include the family history, which is consistent with autosomal dominant inheritance (with 50% chance of transmission to offspring), and the hypersensitivity to sulphonylureas.

The commonest type of MODY (MODY 3) is due to mutation in the HNF1alpha gene, which encodes a transcription factor involved in beta cell development. Other HNFs are implicated in further types of MODY, and in general the hyperglycaemia in these subtypes is progressive, with 30-40% requiring insulin, and risk of microvascular complications which is commensurate with that in type 1 diabetes, matched for glycaemia. Glucokinase mutations reset the set point for glucose homeostasis, and tend to result in mild, non-progressive hyperglycaemia, with low risk of complications.

‘Bright white’ signal on T2-weighted MRI in phaeochromocytoma

The image reveals a large left suprarenal mass. The appearances are typical of a phaeochromocytoma which, unlike most other adrenal tumours, demonstrates a distinctive ‘bright white’ signal on T2-weighted MRI.

In Cushing’s disease (corticotroph pituitary adenoma) bilateral adrenal hyperplasia may be seen on adrenal imaging.

Phaeochromocytoma is one component of the M.E.N. type 2 syndrome (medullary thyroid carcinoma, phaeochromocytoma, parathyroid hyperplasia) and not the M.E.N. type 1 syndrome (parathyroid hyperplasia, pancreatic tumours, pituitary tumours).

Hirsutism

The commonest causes of hirsutism are idiopathic (no cause known), familial / racial, and the polycystic ovarian syndrome (PCOS).

The PCOS usually presents with gradual onset of hirsutism and weight gain on a background of long-standing oligomenorrhoea, typically dating back to puberty.

Virilizing tumours (ovarian or adrenal) are much less common, but should be suspected if there is a sudden onset of symptoms, when examination should look specifically for signs of virilization (male pattern muscle development, clitoromegally).

Androgen Excess

There may be several causes. Important differentials should include:

• polycystic ovarian syndrome (PCOS)
• androgen-producing adrenal and ovarian tumours
• congenital adrenal hyperplasia (CAH)
• Cushing's syndrome.

Congenital adrenal hyperplasia (CAH)

Fig 1: Congenital Adrenal Hyperplasia

Fig 2: Congenital Adrenal Hyperplasia Female

Fig 3: In the adrenal gland, cholesterol is turned into a precursor called pregnenolone, then several enzymes complete the production of aldosterone, cortisol and androgens. A deficiency in the enzyme 21-hydroxylase leads to inadequate amounts of aldosterone and cortisol (green); other substances that do not need the defective enzyme are produced in excess (blue). This enzyme deficiency is inherited and is the most common cause of congenital adrenal hyperplasia (CAH).

Estimation of 17-OH progesterone is relevant regarding CAH but the levels may be raised in certain other adrenal conditions. Short synacthen test, involving estimation of 17-OH progesterone alongside cortisol in response to synacthen, is the standard test for adult type CAH.

Cushing's Syndrome

Fig 4: Signs of Cushing's Syndrome

Menstrual irregularities, hirsutism with virilisation and weight gain are features that may be present in Cushing's syndrome, hence estimation of 24 hours urinary free cortisol on at least two occasions is a good screening test.



Estimation of serum testosterone, other androgens, sex hormone binding globulin (SHBG) and free androgen index (FAI), will be important in all of the above conditions as hyperandrogenism may be present in all of them.

Imaging of adrenals and ovaries, such as CT or MRI scans, is relevant in the above setting but obviously there will be some further indications on basic examination and investigations to suggest the possibility of adrenal tumour, hyperplasia or ovarian tumour.

Estimation of gonadotrophins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) along with androgens and estrogen, is important in the given presentation but there is no indication to perform a gonadotrphin-releasing hormone test. This test is done as a part of the combined triple test in suspected hypopituitarism and in the investigation of delayed puberty.

Fig 1, Fig 2, Fig 3, Fig 4,

Pituitary Adenoma

High prolactin levels may be seen in prolactinomas or any other pituitary or non-pituitary tumours where pressure from the tumour mass on the pituitary stalk functionally disconnects the inhibitory input from the hypothalamus. Some growth hormone secreting adenomas also secrete prolactin.

Low levels of certain pituitary hormones occur due to local effects of the pituitary adenoma (whether secretory or non-secretory). Secondary hypothyroidism due to lack of thyroid-stimulating hormone (TSH), adrenocortical deficiency due to lack of adrenocorticotrophic hormone (ACTH), low IGF-1 associated with growth hormone deficiency and low testosterone associated with FSH and LH deficiency (hypogonadotrophic hypogonadism) can all occur together, in different combinations or on their own.