Inappropriate Secretion Of TSH Research Articles

A case of hyperthyroidism caused by the syndrome of inappropriate secretion of thyroid stimulating hormone. Association of primary hypergonadotropic hypogonadism.

A 49-year-old man with hyperthyroidism caused by the syndrome of inappropriate secretion of TSH (SITSH) is reported. A diagnosis of infertility and hypospermatogenesis due to primary hypergonadotropic hypogonadism had been made 10 years ago. Serum TSH levels were inappropriately elevated with thyrotoxic high levels of thyroid hormone in serum, but no tumorous mass was demonstrated in the pituitary gland. The non-tumorous pituitary resistance of TSH to thyroid hormonal suppression was confirmed by low levels of glycoprotein alpha-subunit and low alpha-subunit/TSH ratios in serum before and after the stimulation by TRH. In addition, the patient had elevated levels of LH and FSH in serum, and their exaggerated responses to LH-RH, although serum testosterone concentrations were normal, indicating primary hypogonadism. It is of interest that SITSH appeared in the hypogonadal patient who was preceded by the long standing hypersecretion of LH and FSH.

FAMILIAL HYPERTHYROIDISM DUE TO INAPPROPRIATE TSH SECRETION: A SEX LINKED DOMINANT TRAIT

Studies in 2 non-related Sephardic Jewish families, one of which extended over 5 generations, revealed 9 females with clinical and/or biochemical hyperthyroidism due to inappropriate TSH secretion. Age at diagnosis ranged from early infancy up to 80 years, the youngest case being detected by measuring elevated thyroid hormones and TSH on a filter paper specimen obtained for routine screening for neonatal hypothyroidism. Except in one case, the clinical manifestations became apparent at adolescence and were more severe in older patients than in younger ones. Yet, these were in general milder than those found in classical Grave's disease. In 4 instances the disorder was diagnosed when symptoms recurred after subtotal thyroidectomy, None had a pituitary tumor. All subjects had elevated levels of thyroid hormones and prolactin (T4: 14-22 ug/dl, T3: 220-320 ng/dl. T3 Uptake: 41-65 %. TSH; 5-26 uU/ml, prolactin: 15-75 ng/ml). TRH further stimulated TSH and prolactin, resembling the response in hypothyroidism. T3 (25 ug/tid) given for one week reduced T4, T3 and TSH (measured 16 h after the last, dose), but T4 (given in equimolar amounts in 2 patients) did not supress any of these parameters. Long term therapy with a single AM dose of T3 (25-50 ug) was given to 6 symptomatic patients. All became clinically and biochemically euthyroid after 3-4 months of therapy, and remained normal since then (up to 7 years). Inappropriate TSH secretion seems to be due to partial unresponsiveness of the thyrotroph to thyroid hormones. The defect may reside in a deficient pituitary T4 monodeiodinase (resulting in low intracellular T3 levels) or in a thyrotroph which has reduced sensitivity to T3. Genetic analysis reveals that X-linked dominance is the most likely mode of inheritance. Calculation of the variance of the expectancy (by the Fisher Exact Test) was highly significant (p= <0.015), indicating that the exclusive prevalence of the mutant gene in females does not occur at random.

CONGENITAL HYPERTHYROIDISM DUE TO INAPPROPRIATE SECRETION OF THYROID STIMULATING HORMONE

The Syndrome of inappropriate secretion of TSH is a rare disease and has been described as a heterogenous group of disorders in juvenile and adult patients who show elevated TSH levels in the presence of elevated thyroid hormone levels.We have observed an infant at age six weeks with congenital goiter who suffered from typical symptoms of hyperthyroidism. In spite of elevated T3 and T4 levels TSH showed basal values between 2 and 8 mU/ml. After TRH-stimulation TSH ranged between 39 and 100 mU/ml. Pituitary adenoma was ruled out; there appeared no relation to Graves' disease.A long term therapeutic trial was performed with the analogue D-thyroxine. TSH gradually returned to normal and the goiter disappeared. After 6 years of observation the physical and psycho-intellectual development and the bone age have been stated to be normal for chronological age, although laboratory data indicated elevated thyroid hormone levels for years.CONCLUSION: Up to now there is evidently no other report on congenital hyperthyroidism due to inappropriate TSH-secretion. Partial pituitary and peripheral thyroid hormone resistance appears to be likely. The long term therapeutic trial with D-T4 has proven to be successful.

HYPERTHYROID GOITRE DUE TO INAPPROPRIATE TSH SECRETION SUCCESSFULLY TREATED WITH DEXTRO-THYROXINE

J.A., a 6 year-old girl with small goitre had elevated levels of T4, T3 as well as TSH. Her high and weight were at the 10th percentile, bone age was delayed about 2 years but clinically she was euthyroid. Treatment with t.h. resulted in TSH suppresion but sings of hyperthyroidism appeared. During the next 3 years without any treatment T4, T3 and basal TSH were still elevated and TRH stimulated TSH increased to the hypothyroid range. At the age of 9 years clinical symptoms of hyperthyroidism were evident. Hypothalamo-pituitary studies were normal, there was no evidence for pituitary tumor. A partial selective pituitary resistance to t.h. was supposed. Since 1980 the patient was treated with D-T4 in a dose of 0.5mg/d. Gradual decrease of TSH levels was accompanied by reduction in the size of goitre and amelioration of clinical symptoms of hyperthyroidism, confirmed by normalisation of BMR. Temporary interruption of D-T4 therapy resulted in -the increase of all clinical and biochemical abnormalities,, To our knowlidge this is the first case of hyperthyroidism due to inappropriate TSH secretion treated with D-T4.

Hyperthyroidism due to non-tumoural inappropriate TSH secretion

Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 micrograms/day). The serum alpha-subunit: TSH molar ratio was less than 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 micrograms injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.

Mild hyperthyroidism with inappropriate secretion of TSH in postmenopausal women.

In a previous study on the function of the hypothalamus - pituitary - thyroid axis, about 10% of postmenopausal women with the climacteric syndrome were found to have borderline high values of T3 and T4 and signs of pituitary decreased sensitivity to the suppressive effect of increased thyroid hormones. The present report concerns 5 women in the first phase of their menopause who showed a mild hyperthyroidism under basal conditions and after suppression test with liothyronine. Each patient had borderline increased levels of serum total and free T4 and T3 and a marked TSH responsiveness to exogenous TRH. After liothyronine, the serum levels of T4, FT4, TSH and the responsiveness to TRH-test clearly decreased. These data suggest an inappropriate TSH secretion with a decreased pituitary sensitivity to thyroid hormones. These cases could represent a modification of the hypothalamus-pituitary-thyroid axis associated with that of the gonadal axis, secondary to the absence of rapid adaptation of neurotransmitters.

Pregnancy with syndrome of inappropriate secretion of TSH

Pregnancy with syndrome of inappropriate secretion of TSH

Familial hyperthyroidism due to inappropriate thyrotropin secretion successfully treated with triiodothyronine.

A family of three generations is described in which six females had hyperthyroidism secondary to chronic overstimulation of the thyroid by pituitary TSH. In the untreated state, their basal levels of T4 ranged between 14-22 microgram/dl, T3 levels ranged from 205-300 ng/dl, T3 resin uptake ranged from 43-61%, TSH ranged from 5-26 microU/ml, and PRL ranged from 33-75 ng/ml. Basal metabolic rate (BMR) was elevated in all patients (+32 to +100%). There was no evidence of pituitary tumor, In spite of elevated circulating thyroid hormones, TRH stimulated TSH and PRL to 25-57 microU/ml and 120-300 ng/ml, respectively. Serum TSH could be suppressed to normal after 1 week of T3 administration (25 microgram three times per day). Concomitantly, serum T3 and T4 levels fell, and the TSH response to TRH became normal. In contrast, T4 (200 microgram/day) administered for 1 and 4 weeks, respectively, to two patients did not suppress the pituitary-thyroidal axis. A long term therapeutic trial was performed in three patients with T3 and a single morning dose of 25-50 microgram. TSH gradually returned to normal, as did thyroid hormone levels and the BMR. The clinical manifestations of hyperthyroidism regressed, and complete remission was achieved after 2-3 months of T3 therapy, which persists to data as long as medication is continued. The inappropriate TSH secretion of our patients appears to be due to partial unresponsiveness of the thyrotroph to thyroid hormone. It is suggested that either the pituitary T4 monodeiodinase is deficient in our patients, resulting in low intracellular T3 levels, or the thyrotroph has reduced sensitivity to T3 and therefore can shut off TSH only when serum T3 is raised to high levels, albeit intermittently.

A Case of The Syndrome of Inappropriate Secretion of TSH

A girl aged 4 years with goiter and accelerated physical and skeletal growth was found to be hyperthyroid on the basis of elevated serum thyroid hormone level, nevertheless both the basal TSH and TSH responsiveness to TRH were maintained within the normal range. Serum TSH was suppressed by exogenous T3 and dexamethasone administration, but not significantly changed after propylthiouracil (PTU) treatment. The diurnal rhythmicity of anterior pituitary hormones was preserved with the high nocturnal peak of TSH and prolactin. Clinically, neither thyrotoxic signs nor evidences of pituitary tumor were observed. Her accelerated growth and elevated thyroid hormone level appeared to be induced by inappropriate secretion of TSH. In view of the literature, this is the first case of the syndrome of inappropriate secretion of TSH excluding the neoplastic origin in Japan.