An overview of thyroid function tests in subjects with resistance to thyroid hormone and related disorders.

Confirmation of sustained syndrome of inappropriate secretion of thyrotropin (SITSH) is a milestone in diagnosis of ß type of resistance to thyroid hormone (RTHß). The differential diagnoses of RTHß include TSH-producing pituitary adenoma (TSHoma) and familial dysalbuminemic hyperthyroxinemia (FDH), which also present SITSH. Recently, patients with RTHα caused by a mutation in thyroid hormone receptor α were reported and they did not present SITSH but a decline in the serum T4/T3 ratio. This review was aimed to overview thyroid function tests in RTH and related disorders. First, the characteristics of the thyroid function in RTHß, TSHoma, and FDH obtained from a Japanese database are summarized. Second, the degrees of SITSH in patients with truncations and frameshifts were compared with those in patients with single amino acid deletions and single amino acid substitutions obtained from the literature. Third, the degrees of SITSH in homozygous patients were compared with those in heterozygous patients with cognate mutations. Finally, the FT3/FT4 ratios in RTHα are summarized. In principle, the TSH values in FDH were within the normal range and apparent FT4 values in FDH were much higher than in RTHß and TSHoma. The FT3/FT4 values in RTHß were significantly lower than in TSHoma. The degrees of SITSH in patients with truncations and frameshifts were more severe than those in patients with single amino acid deletions and single amino acid substitutions, and those in homozygous patients were more severe than those in heterozygous patients with cognate mutations. The FT3/FT4 ratios in RTHα were higher than 1.0.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome.

OBJECTIVE: The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. MATERIALS AND METHODS: We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. RESULTS: The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. CONCLUSION: Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome

ABSTRACT Objective The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. Materials and methods We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. Results The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Conclusion Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

[Syndromes of resistance to thyroid hormone and inappropriate secretion of TSH (SITSH)].

Resistance to thyroid hormone (RTH) is a syndrome in which the responsiveness of end organs to thyroid hormone (TH) is reduced. Given that the TH-responsive end-organs include pituitary thyrotrophs, almost all patients with RTH manifest unsuppressed thyrotropin (TSH) despite elevated free-T4 and free-T3 levels. This abnormal finding in the thyroid function test is termed "syndrome of inappropriate secretion of TSH" (SITSH) or "central hyperthyroidism". Patients with TSH-secreting pituitary tumors(TSHoma) also manifest SITSH. Thus, the differential diagnosis of RTH vs. TSHoma is sometimes difficult and challenging. In this review article, the etiology of RTH and diagnostic approach for SITSH are explained and an algorithm for differential diagnosis of RTH vs. TSHoma is proposed.

Pituitary testing: a reappraisal.

Due to the pulsatile pituitary hormone secretion, their involvement in the acute stress response and feed-back with peripheral hormones, baseline pituitary hormone levels may overlap among normal and pathological subjects. Therefore, dynamic testing has been widely used for the diagnosis and follow-up of pituitary diseases. An ideal test should be sensitive, specific, well tolerated, easy to be standardized and performed and cost-effective. Emerging issues are cost and widespread availability of ultrasensitive hormone assays, increased knowledge of the pathophysiological and pharmacological mechanisms regulating pituitary function and need for better discrimination between clinically useful tests and research tools. In this special issue experts from US and Europe practically approached testing in specific pituitary diseases in the context of current guidelines. Drug effects on different axes are discussed since pharmacologic treatments may influence testing outcome.

Thyroid color flow Doppler sonography: an adjunctive tool for differentiating patients with inappropriate thyrotropin (TSH) secretion due to TSH-secreting pituitary adenoma or resistance to thyroid hormone.

BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone (RTH) are two forms of inappropriate TSH secretion. Thyroid blood flow is largely TSH dependent. OBJECTIVE: To assess whether thyroid blood flow may help to differentiate TSHoma and RTH. DESIGN: Intrathyroidal color flow Doppler sonography (CFDS) pattern and peak systolic velocity (PSV) were assessed at baseline and during T(3) suppression test on eight consecutive patients with TSHoma and 10 with RTH. MAIN OUTCOME: All controls had CFDS pattern 0. Three RTH patients had pattern I and seven had pattern II. Two TSHoma patients had pattern I, five had pattern II, and one had pattern III. PSV at baseline was 3.8 +/- 1.3 cm/s in controls, 8.8 +/- 2.5 cm/s in RTH, 11.1 +/- 2.7 cm/s in TSHoma (p < 0.0003 vs. controls, p = 0.087 RTH vs. TSHoma). After T3 suppression test, PSV values were lower in RTH than in TSHoma (4.6 +/- 1.8 vs. 7.7 +/- 2.6 cm/s, p = 0.008). PSV values and CFDS pattern normalized in nine and eight RTH patients, respectively, after T(3) suppression test; conversely, only one TSHoma patient had a normalization of PSV values, and none had a normalization of CFDS pattern (p < 0.003 vs. RTH). CONCLUSIONS: Both RTH and TSHoma have increased CFDS pattern and PSV values; however, after T(3) both parameters normalized in most patients with RTH but not in those with TSHoma. Accordingly, CFDS pattern and PSV are adjunctive tools to differentiate these two forms of inappropriate TSH secretion.

[Neuroendocrine dysfunction in female patients with systemic dysplasia of the connective tissue]. / Neiroéndokrinnaia difunktsiia u zhenshchin s sistemnoi displaziei soedinitel'noi tkani.

The study covered 119 women with systemic undifferentiated dysplasia of the connective tissue (DCT) aged 14-39 years. All the examinees had vegetative disorders, 26.1% had a neuroendocrine-metabolic form of hypothalamic syndrome (HS), 51.3%--premenopausal syndrome, 65.5%--dysmenorrhea. It was found that women with DCT and HS develop symptoms of neuroendocrine disorders at earlier age than those with HS but free of DCT. Arterial hypertension was registered in 96.8% of patients with DCT and HS, 80.3% of DCT patients with premenopausal syndrome. Central hemodynamics was different in DCT patients without neuroendocrine disorders and with neuroendocrine dysfunction evidencing the role of the latter in development of arterial hypertension in DCT.

Hyponatremia in a pediatric stroke patient: syndrome of inappropriate antidiuretic hormone secretion or cerebral salt wasting?

OBJECTIVE: To determine the potential role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the pathogenesis of cerebral salt wasting. DESIGN: Clinical case report. SETTING: Regional pediatric intensive care unit. PATIENT: A 3-yr-old boy with a cerebral infarct secondary to traumatic carotid artery dissection who developed hyponatremia associated with weight loss and excessive renal sodium excretion on the sixth day after hospitalization. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of ANP, BNP, antidiuretic hormone, and renin were determined serially and compared with concentrations measured in a group of eight healthy children undergoing elective surgical procedures. Compared with controls, ANP and BNP plasma concentrations on the eighth day after hospitalization were increased 1.9-fold and 7.7-fold, respectively. Thereafter, the course of ANP and BNP paralleled that of sodium and H2O excretion and remained elevated until the 14th (BNP) and 16th (ANP) days after hospitalization. Serum antidiuretic hormone and renin concentrations were within normal ranges during the entire observation period. CONCLUSION: Cerebral salt wasting is associated with elevated plasma concentrations of ANP and BNP. Natriuretic peptides may play a role in the pathogenesis of this syndrome.

Hyperfunction and hypofunction in the anterior pituitary.

The actions and interactions of the pituitary gland and the nervous system constitute a regulatory system whereby the physiologic activity of the thyroid, adrenals, and gonads is controlled. Damage to or interference with the pituitary gland may cause hyper- or hypofunctional states resulting in devastating changes in a person's body and life. This article limits its discussion to several of the more frequently encountered pathological states, their diagnostic work-up, evaluation, and treatment.

Marginal and folliculo-stellate cells of the pituitary gland of the rat. A comparative morphometric study in lactating animals.

We examined non-granulated pituitary cells (folliculo-stellate cells and anterior and posterior marginal cells of the pituitary cleft) in lactating and virgin female rats by means of electron microscopy and morphometry. Ultrastructure and morphometric parameters of the cells lining the pituitary cleft were similar in the two groups of animals. On the contrary, folliculo-stellate cells showed a marked nucleocytoplasmic activation in lactating rats in the electron microscope, which was confirmed by morphometric measurements. These results are not consistent with the hypothesis that the three cell types share the same reactivity during pituitary hyperfunction and that they have a common function, as suggested by purely morphological studies in various endocrine conditions. We believe that quantitation of cell response during such stimuli could be useful to further elucidate this matter.

[Circadian rhythm of the pituitary-adrenal system in rheumatoid arthritis]. / K voprosu tsirkadnoi periodichnosti gipofizarno-nadpochechnikovoi sistemy pri revmatoidnom artrite.

Two hundred and fifty-five patients with rheumatoid arthritis (RA) were examined for the levels of free cortisol and corticotrophin as well as for their circadian rhythms. It was established that the lowering of the daily average cortisol level and corticotrophin elevation in the blood as well as the desynchronization types of circadian rhythms depended on the RA gravity and the disease clinical variety. The most pronounced decrease in the cortisol level and destabilization of pituitary-adrenal function were found in the visceral RA pattern, particularly in subjects treated with corticosteroids and in those with hormone-dependent RA. Triamcinolon gave rise to a more substantial lowering of free cortisol as compared to prednisolone. It is assumed that impairment of the synchronization role of hypothalamic formations is of importance in the genesis of neuroendocrine dysfunction in RA patients.