TRH Stimulation Testing in Older Individuals with Persistent Subclinical Hypothyroidism: A Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration

Background: Subclinical hypothyroidism is common in older individuals. To better understand the underlying physiology, we examined the pituitary-thyroid axis using thyrotropin releasing hormone (TRH) stimulation testing both at baseline and after levothyroxine (LT4) and liothyronine (LT3) supplementation. Methods: We conducted a randomized, double-blind, cross-over study in men and women aged 70 years and over without anti-thyroid peroxidase antibodies with persistent subclinical hypothyroidism, defined as having a TSH level between 4.5 and 19.9 µIU/mL with a normal free thyroxine (FT4) level at two consecutive time points. The primary outcome measures were TSH serum concentration area under the curve (AUC), maximum TSH serum concentration (Cmax), and change in free thyroxine (∆FT4) and total triiodothyronine (∆TT3) levels following TRH stimulation, each measured at three time points: once at baseline and once each after achieving euthyroid TSH levels with the two thyroid preparations. The maximal change in TSH (∆TSH); FT4 and TT3 AUCs; and time to maximal TSH, FT4, and TT3 (Tmax) were also analyzed. Results: Thirteen participants [mean (SD) age 77 (5) years], 4 women and 9 men, completed TRH stimulation testing at baseline and after achieving a TSH level of 0.5-1.5 µIU/mL with each therapy. Baseline mean TSH was 4.84 (1.29) µIU/mL. The mean LT4 dose was 105 (36) µg/day and LT4 dose was 34 (9) µg/day. After TRH stimulation, the mean TSH AUC (0-180) at baseline was 3099.5 (1424.4) µIU*min/mL, and significantly decreased after both LT4 [631.4 (315.2), p<0.001] and LT3 [631.5 (317.3), p<0.001]. There was no difference in TSH AUC (0-180) between LT4 and LT3 treatment arms. Baseline mean TSH Cmax was 27.2 (14.5) µIU/mL and significantly decreased after LT4 [5.5 (3.0), p<0.001] and LT3 [5.4 (2.9), p<0.001], with no difference between the LT4 and LT3 treatment arms. The ∆FT4 was 0.11 (0.07) ng/dL at baseline and decreased significantly on LT3. The ∆TT3 was 0.32 (0.09) ng/mL at baseline and significantly decreased on both LT4 and LT3, with no difference between treatment arms. Conclusions: Older individuals with antibody-negative persistent subclinical hypothyroidism have a heterogeneous TSH response to TRH stimulation. Our data show a significantly diminished response to TRH stimulation after thyroid hormone replacement, and they support the pharmacodynamic equivalence of LT4 and LT3 treatment.

Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test

BackgroundThe relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy.MethodsWe retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3).ResultsIn groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy.ConclusionsGH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

Can Endocrine Dysfunction Be Reliably Tested in Aged Horses That Are Experiencing Pain?

The aim of the present study was to evaluate (i) the effects of different intensities and types of treated pain on the basal concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and (ii) the thyrotropin-releasing hormone (TRH) stimulation test, to determine whether treated pain caused a marked increase of ACTH, which would lead to a false positive result in the diagnosis of pituitary pars intermedia dysfunction (PPID). Methods: Fifteen horses with treated low to moderate pain intensities were part of the study. They served as their own controls as soon as they were pain-free again. The horses were divided into three disease groups, depending on their underlying disease (disease group 1 = colic, disease group 2 = laminitis, disease group 3 = orthopedic problems). A composite pain scale was used to evaluate the intensity of the pain. This pain scale contained a general part and specific criteria for every disease. Subsequently, ACTH and cortisol were measured before and after the intravenous application of 1 mg of TRH. Results: There was no significant difference in the basal or stimulated ACTH concentration in horses with pain and controls, between different pain intensities or between disease groups. Descriptive statistics, however, revealed that pain might decrease the effect of TRH on the secretion of ACTH. There was an increase of ACTH 30 min after TRH application (p = 0.007) in the treated pain group, but this difference could not be statistically confirmed. Measuring the basal ACTH concentration and performing the TRH stimulation test for the diagnosis of PPID seem to be possible in horses with low to moderate pain.

MON-478 Impaired Sensitivity to Thyroid Hormone - A Diagnostic and Therapeutic Challenge

Background: Impaired sensitivity to thyroid hormone refers to any process that negatively affects its action, including defects in its transport, metabolism and action on the receptor. Resistance to thyroid hormone due to beta-receptor mutations (RTH-beta) is the most common form of this entity and is characterized by reduced response of peripheral tissues to the action of thyroid hormone. The genetic variability of cofactors involved in the action of thyroid hormone explains the heterogeneity of resistance among affected individuals. Generally, patients with this disorder, have increased levels of free T4 and free T3 in association with normal or high TSH. Clinical case: 11-year-old boy, with personal history of Attention-deficit/hyperactivity disorder (ADHD). A pediatric endocrinology consultation was requested to evaluate abnormalities in his thyroid function tests. A few months earlier, his father was referred to endocrinology consultation because of thyroid function tests abnormalities: TSH - 3.01 μIU / mL (N: 0.35 - 4.94); Free T4 1.7 ng / dL (N: 0.7-1.48); Free T3 4.77 pg / mL (N: 1.71-3.71). Initially, two diagnostic hypotheses were considered: central hyperthyroidism or impaired sensitivity to thyroid hormone. The adult underwent pituitary magnetic resonance, which raised the hypothesis of a pituitary microadenoma, and TRH stimulation test, whose result was strongly suggestive of the second diagnostic possibility. A genetic study was requested and the presence of the c700 G> A variant (p. Ala 324 trh) in the THRB gene was identified, which confirmed the most likely hypothesis. At the time of the pediatric endocrinology consultation, the 11-year-old boy had the results of his lab tests: TSH - 6.67 μIU / mL (N: 0.35 - 5); T4L 2.27 ng / dL (N: 0.88-1.58); T3L 7.79 pg / mL (N: 2-4.20). Given his perfect height and weight evolution and the absence of symptoms suggestive of hypo or hyperthyroidism, it was decided not to start any medication, keeping only periodic surveillance. Conclusion: This case exemplifies unusual thyroid function tests. This discordance between serum thyroid hormone and TSH concentrations should raise the possibility of impaired sensitivity to thyroid hormone. In this condition, patients may present with symptoms of hypo or hyperthyroidism and the etiology of thyroid function tests abnormalities are not easily recognized. This can lead to misdiagnosis and consequently unnecessary treatment.

Subclinical hypothyroidism & infertility: a review

Subclinical hypothyroidism (SCH) may be of greater clinical importance in women with “unexplained” infertility, especially when the luteal phase is inadequate, and such patients should be investigated for thyroid dysfunction in detail. To date, studies investigating the association between SCH and infertility are still based on the high serum thyroid stimulating hormone (TSH) levels while some older studies are based on the presence of an abnormal serum TSH after a thyrotropin releasing hormone (TRH) stimulation test. The recommendation in the current guidelines to treat subclinical hypothyroidism is based on minimal evidence and it is thought that with treatment the potential benefits outweigh the potential risks. Thyroxine-replacement therapy should be started in patients with SCH caused by conditions which are at high risk of progression to overt hypothyroidism.Ibrahim Med. Coll. J. 2014; 8(1): 17-24

Extensive investigation of 114 patients with Sheehan's syndrome: a continuing disorder

ObjectiveSheehan's syndrome (SS) is a well-known cause of hypopituitarism resulting from postpartum pituitary necrosis. Because of its rarity in Western society, its diagnosis is often overlooked. We aimed to investigate the clinical, laboratory, and radiological aspects of SS in a large number of patients.Study designA retrospective assessment of the medical records of 114 patients with SS was conducted. In addition, sella turcica volumes of 29 healthy women were compared with those of patients by magnetic resonance imaging examinations.ResultsThe mean period of diagnostic delay was 19.7 years in patients with SS. It was found that 52.6% of patients had nonspecific complaints, 30.7% had complaints related to adrenal insufficiency, and 9.6% had complaints related to hypogonadism when diagnosed. At the time of diagnosis, 55.3% of the patients had panhypopituitarism, while 44.7% had partial hypopituitarism. The number of deficient hormones was found to be increased over the years. None of the patients whose basal prolactin was below 4.0 ng/ml had adequate prolactin responses to TRH test, while all patients whose basal prolactin was above 7.8 ng/ml had adequate responses. Mean sella volume was found to be significantly lower in the SS group (340.5±214 mm3) than that in the healthy group (602.5±192 mm3).ConclusionsSS is a common cause of hypopituitarism in underdeveloped and developing countries. The main reasons for diagnostic delay seem to be the high frequency of patients with nonspecific complaints and neglect of SS. In addition, the TRH stimulation test was found to have a high sensitivity and specificity to recognize PRL deficiency. Furthermore, small sella size may have an important contributing role in the etiopathogenesis of SS.