Clinical Signs Of Hypothyroidism Research Articles

Lingual thyroid ectopia

The lingual thyroid gland is an abnormal mass of ectopic thyroid tissue visible at the base of the tongue, caused by an embryological anomaly in the development of the thyroid gland. Identification and symptom-adapted treatment of ectopia are important in preventing hypothyroidism and development of obstructive symptoms. Purpose. To present a case of lingual ectopia of the thyroid gland in a child with an incidentally diagnosed formation of the root of the tongue based on primary ultrasound diagnosis. Material and methods. A 7-year-old boy without clinical signs of hypothyroidism during a routine examination revealed a voluminous asymptomatic formation of the root of the tongue. Results. Along the midline at the root of the tongue there is a rounded, non-displaced, painless formation about 20 mm in diameter. Regional lymph nodes are not enlarged. The picture of ectopic thyroid tissue in the root of the tongue, in the absence of thyroid in a typical site on the neck. There is subclinical hypothyroidism with a TSH level of 12.8 mсME/mL (normal 0.6–4.84). The presence of ectopia was confirmed by scintigraphy with Technetium-99m pertechnetate. Normal TSH level of 3.37 mcME/mL and a reduction in the volume of ectopic thyroid tissue from 3.3 mL to 2.13 ml revealed 3 months after levothyroxine therapy at a dose of 50 mcg/day. Conclusion. Ultrasound exam with Doppler mapping is mandatory and allows not only to identify ectopic tissue, but also to identify the absence of thyroid in a typical anatomical area on the neck. The study of the hormonal profile and subsequent scintigraphy make it possible to make a final diagnosis, assess the function of the ectopic organ and determine the option of drug and/or surgical treatment.

Osteoartropathies associated with hypoteriosis in endemic goiter in sheep in the Republic of Khakasia

The article discusses the issues of changes in the state of the musculoskeletal system, in particular the skeletal system, in ewes and lambs with thyroid pathologies with iodine deficiency, kept in the conditions of peasant farms in the Beisky district of the Republic of Khakassia. The results are obtained from 20 ewes and their lambs with severe thyroid hyperplasia, for the period from 2020 to 2021. In the study of sheep using clinical, biochemical and radiological methods of research, they turned to the clinical status of animals with details on the musculoskeletal system: the state of muscles, joints, bones. As a result of the research, it was found that system-wide deviations in the body of sheep with endemic goiter and hypothyroidism are caused by the complex effect of iodine deficiency, against the background of an increased content of fluorine, cobalt, calcium in animal feed and water, which is due to being in an ecologically unfavorable zone. Endemic goiter and hypothyroidism occurs in adult sheep in a latent form and is clinically expressed in their offspring. Clinical signs of hypothyroidism in lambs are expressed by the development of myxedema, the development of myopathies and osteoarthropathy, caused by disturbances in oxidative processes and thermogenesis in the body. X-ray signs of thyroid osteoarthropathies are expressed by a slowdown in osteogenesis, especially epiphyseal growth zones of the type of punctate dysplasia, more pronounced on the pelvic limbs, the presence of moderate osteoporosis with an elevated level of calcium in the blood. The established biochemical abnormalities in blood parameters are characterized by an increase in the level of liver enzymes: ALT, AST, alkaline phosphatase and are directly proportional to the severity of clinical signs and the degree of thyroid hyperplasia.

Canine hypothyroidism: avoiding over diagnosing the condition

Background: Hypothyroidism is one of the most commonly treated endocrine disorders in dogs; however, the diagnosis of this condition can be challenging, potentially leading to misdiagnosis. The clinical signs of hypothyroidism are vague and non‐specific, as are the routine haematological and biochemical changes. When assessing the thyroid axis, the classical finding of decreased total thyroxine and increased thyroid‐stimulating hormone is highly specific for the diagnosis of hypothyroidism, but has less good sensitivity. Although numerous other tests are available, a basic understanding of thyroid gland physiology and thyroid test methodology is needed to be able to use each test and interpret the results correctly.Aim of the article: This article discusses how to confidently diagnose the condition, explaining how clinicians need to consider the clinical signs, routine clinicopathological changes and thyroid hormone concentrations together, rather than in isolation.

Thyroid Disorders.

Thyroid Disorders.

Use of “Kayod” Preparation in Cows

The Altai territory is an agricultural region; it is a biogeochemical province deficient in iodine. We conducted a study of metabolic disorders in cows that had hypofunction of the thyroid gland. Our research is devoted to the expediency of a single use of the drug “Kayod” administered in the form of a subcutaneous implant in order to normalize the therapeutic status of animals suffering from a chronic lack of iodine in their diet. The purpose of this work is to justify not only the use of the preparation “Kayod” in animals kept in the biogeochemical provinces deficient in iodine, but also the use of tablets administered through a subcutaneous implant. We found a significant increase in the amount of hemoglobin and a decrease in the number of white blood cells in the blood of animals after the use of “Kayod”, and in the second experimental group, these indicators were slightly higher than in the first one. Indicators of the level of total protein and reserve alkalinity of blood were within the limits of physiological norms, but in the experimental groups they were slightly higher than in the control group. The level of total calcium and carotene in the blood of animals in the experimental groups, especially the second, significantly exceeded the level of the same substances in the blood of the animals in the control group. However, the level of inorganic phosphorus tended to decrease. The level of glucose in the blood of cows in the experimental group increased significantly more than in the blood of cows in the control group. This increase was particularly significant in the blood of animals in the second experimental group. When the preparation “Kayod” was used in the form of a subcutaneous implant, there were no clinical signs of hypothyroidism in the cows of the first experimental group after nine weeks. In the cows of the second experimental group, the condition of the cows returned to normal after six weeks.
 Keywords: Cows, iodine, hypothyroidism, implant, “Kayod

Clinical signs of hypothyroidism in domestic dogs

The research was conducted during 2016–2019 on the basis of veterinary clinics in Poltava - veterinary clinic at the Department of Therapy named after Professor P.Lokes of Poltava State Agrarian Academy, “Vet Line”, “Vet Comfort” and the laboratory of the Department of Therapy named after Professor P. I. Lokes of Poltava State Agrarian Academy. During the research we studied 11 dogs, which were diagnosed with hypothyroidism. The animals belonged to different breeds, had different sexes (6 females and 5 males) and age. For control we took 15 dogs without visible signs of any pathology. We compared the breed susceptibility of dogs with hypothyroidism and dogs with alimentary obesity. Thus, we found that most breeds are common to animals in both pathologies. However, in our sample for hypothyroidism there was no such breed as a pug, and outbred individuals, which accounted for a significant percentage of dogs with alimentary obesity. One of the most common clinical symptom is the presence of symmetrical alopecia on the sides on the background of dull and disheveled hair (90.9 %). Mucosal anemia was observed in a significant proportion of animals (81.8 %). The symptom of bradycardia and shortness of breath during exercise is observed in 72.7 % of experimental animals, which indicates the development of pathological changes in the cardiovascular system. It was found that all animals showed depression, weakness and fatigue (100.0 %). Polydipsia and hypothermia were much less common in 45.5 % of dogs, and corneal dystrophy in 36.4% of cases. The last clinical manifestation occurred in animals with the most severe pathology. According to the literature, it is known that hypothyroidism in dogs is often a symptom of obesity. According to our data, obesity (overweight) was registered in 63.6 % of experimental animals. With the diagnosis of “hypothyroidism” in dogs, we identified two experimental groups: 1 – animals with normal fatness; 2nd – with a clinical symptom of obesity. We can note a significant increase in adipose tissue in dogs with hypothyroidism of the 2nd experimental group (45.1 ± 1.70 %), which indicates the presence of endocrine obesity, as evidenced by visual assessment of fatness (4.7 ± 0.18 points). Such changes develop due to insufficient production of thyroid hormones. The latter play an important role in regulating metabolism in the body. Due to their deficiency, the metabolism in animals slows down and, as a result, there is a risk of obesity.

Undiagnosed hypothyroidism with delayed recovery: A case report.

Sir, We report a case of delayed recovery from general anesthesia, which was later on diagnosed as a case of hypothyroidism. A 60-year female patient was posted for elective open cholecystectomy with heart rate 47/min, blood pressure 140/80 mmHg, and normal electrocardiograph. Patient had no other comorbidities and was not any drugs. Her echocardiography revealed stage I left ventricular diastolic dysfunction with normal systolic functions. Medicine referral was done for bradycardia. On operating table (OT) table, her heart rate (HR) increased to 58/min after injecting atropine 0.6 mg intravenously (IV). Anesthesia was induced with intravenous morphine, thiopentone, and vecuronium with endotracheal intubation and maintained with isoflurane, nitrous oxide, and oxygen uneventfully. At the end, patient recovered well with adequate spontaneous respiration and neuromuscular blockade was reversed with injection neostigmine and glycopyrrolate. However, following extubation, patient became drowsy and apneic. Trachea was reintubated and intermittent positive pressure ventilation was restarted. Fresh reports revealed normal electrolytes and blood gas analysis. Patient was re-evaluated clinically and was observed to have very thick and rough skin (probably missed in preanesthetic evaluation), low body temperature, and bradycardia without thyroid swelling. Suspecting hypothyroidism, blood sample was sent for TSH estimation after 2.5 h of reintubation; and as injectable thyroxine was not available, two tablets of Thyroxin 100 μg each were given through Ryle's tube empirically on emergency basis. Patient recovered well after 4 h of elective postoperative ventilation. She became conscious with adequate spontaneous ventilation. Trachea was extubated. After surgery, corticosteroid replacement therapy was started as 100 mg three times a day and continued as oral therapy, since hypothyroidism is commonly associated with adrenal insufficiency. Her diagnosis was later confirmed as hypothyroidism after receiving reports of TSH level (TSH: 111 μIU/L). She was put on tablet Eltroxin 100 μg daily thereafter. Hypothyroidism may be present in subclinical form. The anesthetic requirement of hypothyroid patients has not been analyzed so far in any study; but clinically, they are found to be more sensitive to anesthetic drugs and sedatives affecting anesthetic management.[12] Clinical signs of hypothyroidism may range from cold intolerance to constipation, depression, lethargy, muscle weakness, slow movement, dry skin, slow gastric emptying, sleep apnea, depression of ventilatory response to hypoxia, and hypercarbia.[3] The normal range of TSH is 0.3–4.5 mU/L. Primary hypothyroidism is diagnosed through detection of a low free T4 and a high TSH level. A rising TSH level is the most sensitive indicator of failing thyroid function.[4] Hypothyroidism causes increased responsiveness to central nervous system depressants and neuromuscular blocking agents. Increased sensitivity may be secondary to reduced cardiac output and blood volume, abnormal baroreceptor function, slowing of drug metabolism, and excretion. Decreased neuromuscular excitability, decreased ventilatory response to hypoxia, and hypercarbia are enhanced by anesthetic agents.[14] Due to depression of vascular and respiratory reflexes, hypotension, cardiac arrest and delayed recovery of spontaneous ventilation is common in hypothyroid patients.[5] Such patients should be rendered euthyroid before the surgery. Regional anesthesia should be preferred, if the surgery cannot be delayed.[5] To conclude, a patient of persistent bradycardia may have other than cardiac cause. In cases of emergency, signs of hypothyroidism may be managed empirically with enteral thyroid hormone replacement state, if parenteral form of thyroxine is not available. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Levothyroxine supplementation in hypothyroid bitches during pregnancy

Hypothyroidism is the most common endocrine disease in dogs and has been shown to have a hereditary nature in many breeds. Previous studies have documented decreased fertility in bitches with experimentally-induced hypothyroidism, decreased viability at birth, increased periparturient mortality, and reduced birth weight in pups born to hypothyroid dogs. Hypothyroid women have an increased demand for exogenous thyroxine throughout gestation in order to maintain normal plasma concentrations of thyroid hormones and produce neuropsychologically normal children. This study was performed to determine if pregnancy causes a similar need for increased levothyroxine dosages in dogs to maintain a euthyroid state. Serum was harvested from blood collected from six bitches with experimentally-induced hypothyroidism that were receiving standard thyroid hormone replacement therapy and from four euthyroid control bitches. Thyroid function tests performed on these samples included total thyroxine (T4), free T4 (fT4), thyroid stimulating hormone (TSH), and 3,5,3′-triiodothyronine (T3). Thyroid function tests were measured from ovulation through the end of pregnancy. All bitches whelped normal litters. Euthyroid bitches had no significant alterations in their hormone concentrations throughout pregnancy. None of the supplemented hypothyroid bitches had clinical signs of hypothyroidism throughout the study. Serum concentrations of T4 and fT4 were elevated compared to ovulation at multiple sample points during gestation in supplemented dogs. The results from this study indicate that standard levothyroxine supplementation is adequate to maintain a euthyroid state during pregnancy in experimentally-induced hypothyroid dogs. In addition, there is no evidence that canine thyroid profiles in euthyroid dogs are altered during gestation.

Severe depression and rhabdomyolysis as “masks” of primary hypothyroidism: clinical cases

Rationale: Primary hypothyroidism is one of the most common endocrine disorders. Difficulties in its diagnosis are related to the lack of specific and pathognomonic clinical symptoms of the disease. It is not infrequent that before the right diagnosis is made, patients with hypothyroidism go a long way of examinations and consultations of various specialists; we have illustrated this by two clinical cases.Clinical case No. 1 was a 69-year old woman with a late diagnosis of severe primary hypothyroidism. Despite the presence of typical clinical signs of hypothyroidism, such as epidermal and edematous syndromes, encephalopathy, depression, and anemia, some clinical patterns (significant weight loss, ascites, low cholesterol, protein, electrolyte levels, and severe anemia) directed the diagnostic search towards oncology. It was the oncologist who was the first to suggest hypothyroidism that was later confirmed by high thyroid-stimulating hormone (TSH) levels.Clinical case No. 2 was a case of hypothyroidism in a young man with a baseline history of kidney disease. Fatigue, myalgia, neurological abnormalities, cytolysis and hypercholesterolemia were the leading symptoms that progressed steadily and led to disability.Conclusion: These clinical cases demonstrate the variety of clinical symptoms in manifest hypothyroidism and emphasize the significance of high awareness of this disorder among various medical specialties. It is of note that laboratory tests to diagnose primary hypothyroidism are very simple and available (high serum TSH level is enough for the diagnosis) and treatment with levothyroxine sodium is very effective.

Depression of the elderly revealing a primary hypothyroidism

Introduction Psychiatric manifestations are exceptional during hypothyroidism and are not always easy to diagnose, especially since the clinical signs of hypothyroidism can be confused with those of the depressive syndrome. We report an original observation of depression of the elderly revealing an isolated primary hypothyroidism. Observation A 78-year-old patient, followed for essential hypertension, well-balanced under monotherapy with calcium channel blockers, and without degenerative complications, was referred by her family doctor for depressive syndrome not improved by the specific treatment prescribed and correctly taken for six months. The clinical examination noted in particular macroglossia with dental impressions and dry and cracked skin. The biological assessment showed hypothyroidism with TSH at 28 μmol/l. Thyroid ultrasound showed atrophy of the thyroid gland. The thyroid autoimmunity (anti-thyroglobulin and anti-thyroperoxidase antibodies) was negative. The rest of the biological tests were in the normal range. The diagnosis of Riedel’s thyroiditis was retained and the patient was treated with levothyroxine in progressive doses until TSH normalization was achieved. The evolution on the psychiatric level was also favorable with disappearance of the signs of the depression and the anti-depressive treatment was discontinued. Conclusion Depression is rare, complicating only 4% of overt hypothyroidism and its diagnosis is not always easy, especially in the elderly. Hormone replacement therapy significantly improves the depressive syndrome and protects against cognitive decline. Thus, hypothyroidism screening seems appropriate for any depressive syndrome in the elderly.

Evaluation Of Hypothyroidism In Β-Thalassemia Major.

The aim of this study was to determinestatus of hypothyroidism ingroup of patients with b-thalassemia major & to know the correlationbetween thyroid function and the degree of iron overload represented by S. ferritin level.The cross-sectional study did 100 cases of b-thalassemia major,50 patient >10 years of age and 50 patient between 5-10 years of age by using the principle of measuring T3,T4,TSH,and serum ferritin combines an enzyme immunoassay competition with a final fluorescent method (ELFA).Total number of patient 100,50 patient >10yr. of age 5 cases (10%) with elevated TSH 5-10µIU/ml & normal T4 who diagnosed as subclinical hypothyroidism & 2cases (4%) with elevated TSH & low T4 who diagnosed as overt hypothyroidism. While another group 50 patient [age < 10 years] of them only there are 4 cases (8%) of subclinical hypothyroidism. Subclinical cases occur in a fraction of those patients in the lack of clinical signs of hypothyroidism. Standard follow-up for early recognition & appropriate treatment of this complication could make life of those patients better.

Repeatability and variability of total T4 measurements at three German veterinary laboratories

To evaluate the reproducibility of serum testing for total thyroxine (T4) in three German laboratories. Serum was taken from 53 dogs with suspected hypothyroidism and divided into five aliquots. Three aliquots of each sample were marked with different names and sent to one laboratory (two aliquots simultaneously and one aliquot 1-3days later). The remaining aliquots were sent to two other laboratories. Laboratory1 used an enzyme immunoassay for T4 measurements, whereas laboratories2 and 3 used a chemiluminescence immunoassay. The agreement between the three laboratories (values within or below the reference interval) was determined using the Cohen's Kappa test. The intra- and interassay variability was calculated for each laboratory and the agreement between samples submitted to the same laboratory was also determined using the Cohen's Kappa test. For n=23/41 patients tested simultaneously in the three laboratories, all three values were either uniformly below, within or above the respective reference interval. The Cohen's Kappa value for intra- and interassay agreement was 1.0 in laboratory2 (n=15, complete agreement), 0.33 in laboratory1 (n=16) and 0.37 (intra-) and 0.19 (interassay agreement) in laboratory3 (n=16, low agreement). There was a low agreement between laboratories1 and 2 and between laboratories1 and 3 (κ=0.30 and 0.25, respectively), while a high agreement was determined between laboratories2 and 3 (κ=0.68). The intrassay variability of laboratories1, 2 and 3 was 13.6%, 5.0% and 10.4%, the interassay variability 17.2%, 5.1% and 17.4%, respectively. The differences in the measurement of thyroxine concentrations of the same serum sample in different laboratories and at different time points in the same laboratory underline the high relevance of interpreting laboratory results in context with the clinical signs of hypothyroidism as well as other laboratory values such as TSH concentration.

Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs.

BackgroundBoth elevated homocysteine and decreased folic acid concentrations are observed in human patients with hypothyroidism and can influence the development of numerous secondary disorders.ObjectivesThe aim of the study was to assess total homocysteine concentration in serum and to examine its relationship with the concentration of folic acid and thyroid hormones (tT4 and fT4).AnimalsTen healthy and 19 hypothyroid client‐owned dogs.MethodsDogs with clinical signs of hypothyroidism had the diagnosis confirmed by additional tests. Total homocysteine, folic acid, total thyroxine, and free thyroxine concentrations in serum were evaluated.ResultsHypothyroid dogs were diagnosed with increased homocysteine (median 22.20 μmol/L; range, 16.50–37.75) and decreased folic acid (median 20.62 nmol/L; range, 10.54–26.35) concentrations, as compared to healthy dogs (11.52 μmol/L; range, 10.00–16.65 and 30.68 nmol/L; range, 22.84–38.52, respectively). In sick dogs, total homocysteine was inversely correlated with folic acid (ρ = −0.47, P < 0.001), total thyroxine (ρ = −0.69, P = 0.0092), and free thyroxine (ρ = −0.56, P = 0.0302).ConclusionsHypothyroidism in dogs causes hyperhomocysteinemia. Concomitant mild folic acid decrease in hypothyroid dogs might be as a result of hyperhomocysteinemia.

Resveratrol has anti-thyroid effects both in vitro and in vivo

Resveratrol is a natural polyphenol with antioxidant, anti-inflammatory, and antiproliferative properties. We have shown previously that resveratrol decreases sodium/iodide symporter expression and iodide uptake in thyrocytes, both in vitro and in vivo. In the present study, we further investigated the effects of resveratrol, with evaluation of the expression of additional thyroid-specific genes in the FRTL-5 rat thyroid cell line: thyroglobulin, thyroid peroxidase, TSH receptor, Nkx2-1, Foxe1 and Pax8. We observed decreased expression of these genes in FRTL-5 cells treated with 10 μM resveratrol. The effects of resveratrol was further evaluated in vivo using Sprague-Dawley rats treated with resveratrol 25 mg/kg body weight intraperitoneally, for 60 days. No clinical signs of hypothyroidism were seen, although the treated rats showed significant increase in thyroid size. Serum TSH and thyroid hormone levels were in the normal range, with significantly higher TSH seen in resveratrol-treated rats, compared with control rats. Histological and immunohistochemical analyses confirmed increased proliferative activity in the thyroid from resveratrol-treated rats. These data suggest that resveratrol acts as a thyroid disruptor and a goitrogen, which indicates the need for caution as a supplement and for therapeutic uses.

THYROID FUNCTION IN DOGS WITH VISCERAL LEISHMANIASIS

Resumo Vários fatores extratireoidianos como idade, raça, doenças concomitantes e fármacos podem influenciar na função e no diagnóstico do hipotireoidismo em cães. As alterações nas concentrações dos hormônios tireoidianos decorrentes de doenças não tireoidianas é denominada de síndrome do eutireoideo doente. O objetivo deste estudo foi avaliar a influência da leishmaniose visceral na função da tireoide em cães sem sinais de hipotireoidismo, com ou sem azotemia. Os animais positivos para leishmaniose foram divididos em seis grupos (albumina nornal ou diminuída, creatinina normal ou elevada, uréia normal ou elevada) e foi avaliado o efeito nesses grupos das concentrações séricas do hormônio estimulante da tireoide (TSH), tiroxina total (TT4) e da tiroxina livre (FT4). Os cães positivos para leishmaniose, pelo teste de ELISA, apresentaram concentrações séricas de TSH mais elevadas do que os animais soronegativos, enquanto que as concentrações de TT4 e FT4 em cães com leishmaniose foram menores (P &lt;0,01) quando comparadas com as dos cães saudáveis. No entanto, os resultados estavam no intervalo dos valores para os animais eutireoideos. Nos cães seropositivos para leishmaniose, a TT4 apresentou diferença estatística significativa (P &lt;0,04) no grupo com hipoalbuminemia em relação ao grupo com normoalbuminemia, respectivamente, 1,01ug/dL e 1,4ug/dL. Concluiu-se que os cães positivos para a leishmaniose visceral não desenvolveram síndrome do doente eutireóide, embora as concentrações de TT4 e a FT4 estivessem reduzida e de TSH elevada em relação aos cães sem leishmaniose.

Thyroxin and progesterone concentrations in pregnant, nonpregnant bitches, and bitches during abortion

Serum progesterone and thyroxin concentrations were measured weekly until 61 to 62 days after ovulation in 24 pregnant bitches and in the control group of nine nonpregnant bitches in the luteal phase. Fourteen of the 24 dogs had a normal pregnancy and parturition. Ten of the 24 dogs showed mucinous or colored vaginal discharge, decreased appetite, or lethargy. These initial signs of abortion or fetal resorption were noted during the fourth week of pregnancy, and the process occurred over the next 2 weeks. Progesterone and thyroxin concentrations were measured by quantitative ELISAs validated to dog serum. The serum progesterone concentrations of the group going through abortions differed significantly from the third week until the end of the eighth week. The mean serum thyroxin concentrations of healthy pregnant and nonpregnant groups significantly exceeded the reference range (20–45 nmol/L). The serum thyroxin concentrations in the abortion group were between 16.15 ± 3.17 and 40.78 ± 8.97 nmol/L. The values in this group were significantly different from the other two groups at the third week of the luteal phase. Clinical signs of abortion or fetus resorption manifested in midpregnancy. The clinical signs of abortion coincided in each case with a low serum progesterone concentration (<10 ng/mL). This phenomenon indicated, in contrast with other studies, that the decrease of serum progesterone below 10 ng/mL at the fourth week of pregnancy may signal impending abortion. In the second half of pregnancy, the thyroid gland was not able to respond adequately to the elevated requirement in thyroid hormone, although in other periods of the ovarian cycle, there were no clinical signs of hypothyroidism.

A TSHβ Variant with Impaired Immunoreactivity but Intact Biological Activity and Its Clinical Implications.

Thyrotropin (TSH) deficiency caused by TSHβ gene mutations is a rare form of congenital central hypothyroidism. Nine different TSHβ gene mutations have been reported, all with clinical manifestations. The aim was to identify the genetic cause of undetectable TSH levels in two siblings with clinical euthyroidism. Two brothers born to consanguineous Pakistani parents presented with undetectable serum TSH but normal iodothyronine concentrations and no clinical signs of hypothyroidism. Direct sequencing of the TSHβ gene, functional and immunological studies, protein homology modeling, and population frequency analysis were performed to characterize the cause of undetectable TSH in this family. Direct sequencing of the TSHβ gene revealed that the two brothers were homozygous for a single nucleotide substitution (c.223A>G) resulting in the replacement of arginine 55 with glycine (R55G). This variant was found in 12 out of 5008 alleles in the 1000 Genomes project (all South Asian). Serum TSH of the two brothers was undetectable in two of five platforms, both produced by Siemens, whereas TSH levels of the heterozygous brother and mother were half compared to the other three platforms (Roche Elecsys, Abbott Architect, and Beckman Coulter DxI). The falsely low TSH concentration was caused by the monoclonal antibody not recognizing the region containing the variant amino acid. This is supported by the fact that arginine modification--following phenylglyoxal treatment--led to a significant (96%) decrease in the TSH measurement with the Siemens platforms. Predictions based on PolyPhen-2 and in silico modeling revealed no functional impairment of the variant TSH. A TSHβ variant with impaired immunoreactivity, but not bioactivity, is reported, and its biochemical impact in the homo- and heterozygous state is demonstrated. It is also shown that failure to bind to the monoclonal antibody is a direct consequence of the amino acid substitution.

Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): Chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding

Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): Chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding

Frequency of other endocrine disorders in hypothyroidism

Hypothyroidism is a condition of reduced production, distribution, or absence of action of thyroid hormones. Clinical diagnosis of hypothyroidism is not easily established due to the nonspecific clinical manifestations. Determination of serum TSH is the first-line test for the diagnosis of hypothyroidism. The aim of the study was to determine the presence of other endocrine disorders in patients with subclinical (TSH levels between 5 and 10 mIU/l), or clinical (TSH above 10 mIU/l) hypothyrodism. We analyzed 50 patients (35 with clinical hypothyroidism and 15 with subclinical form). In all patients anthropometric data (age, sex, weight, height, body mass index, blood pressure and heart rate), and clinical signs of hypothyroidism (skin changes, menstrual disorders) were determined. Blood was drawn in fasting state for measurement of FT4, sTSH, glucose, lipids, ionized calcium, PTH, cortisol, ACTH, prolactin, gonadotropins, estradiol in women of reproductive age, and testosterone in men. Skin lesions were rarely present. Oligomenorrhea was more frequent in subclinical hypothyroidism, and menopause in clinical hypothyroidism. Blood pressure was normal in all subjects. Patients with clinical hypothyroidism compared to those with subclinical form had higher TSH values (19.5 ± 5.7 vs. 5.9 ± 0.3 mIU/l), and higher doses of L-thyroxine (81.2 ± 4.6 vs. 21.4 ± 3.5 μg/day). Disturbance of glycemic control was present in 18% of patients. Total cholesterol and LDL were insignificantly higher in patients with hypothyroidism than in subclinical form of the disease. FT4, calcium, PTH, cortisol, ACTH, gonadotropins, estradiol and testosterone did not differ between groups. The proatherogenic relation of estradiol with triglycerides was established in women with clinical form of hypothyroidism.

Can Quetiapine-Induced Hypothyroidism be Reversible Without Quetiapine Discontinuation?

Recent clinical trials and case reports have recorded dose-related thyroid function test abnormalities during quetiapine treatment usually requiring drug discontinuation or initiation of thyroid replacement therapy. The authors highlight the potential reversibility of quetiapine-induced hypothyroidism without quetiapine discontinuation in 2 in-patients (a 51-year-old schizophrenic woman and a 46-year-old bipolar man) to which quetiapine (300 and 350 mg/d, respectively) was administered. Both patients had a negative personal and family history of thyroid dysfunction. Significant decreases in T4/free T4 levels and a marked elevation in thyroid-stimulating hormone level were recorded without any clinical signs of hypothyroidism 3 weeks after quetiapine initiation. Antithyroid antibody titers remained within reference range. Thyroid function tests returned to normal 6 weeks after quetiapine initiation, although quetiapine was continued at the same daily dose without thyroid replacement therapy. These are the first cases reporting spontaneous resolution of quetiapine-induced hypothyroidism without quetiapine discontinuation. We suggest careful thyroid monitoring for patients initiating quetiapine. However, physicians can wait in cases of quetiapine-induced hypothyroidism if a close laboratory monitoring is available because thyroid dysregulation may soon resolve.