Severe Primary Hypothyroidism Research Articles

Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia.

Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

Myxedema Coma: A Rare Case Report of Severe Hypothyroidism in Uganda

Objective: in this report, we describe a case of myxedema coma in a 46-year-old Ugandan lady who had never before had hypothyroidism. Investigations and Medical Care: The patient's first presentation included bradycardia, hypothermia, and a noticeably low Glasgow Coma Scale score. Laboratory examinations revealed severe primary hypothyroidism. Intravenous levothyroxine, hydrocortisone, and supportive care were the first steps in the treatment. Results: After receiving therapy for one week, the patient achieved a full recovery. Thyroid function tests showed improvement back to normal range. Conclusion: This case highlights the importance of considering myxedema coma in the differential diagnosis of altered mental status, even in resource-limited settings. Increased awareness, prompt diagnosis, and appropriate treatment can be life-saving in these cases.

The Dramatic Outcome of the Late Diagnosis of the Chronic Autoimmune Thyroiditis with the Severe Primary Hypothyroidism

The article is devoted to the analysis of a clinical case of the severe hypothyroidism. A review of the “clinical masks” of the hypothyroidism is presented. The examination of the polymorbid patients should include the level of thyroid-stimulating hormone and thyroid hormones. The untimely initiation of substitution therapy is associated with a poor prognosis, and the early start of the treatment is a guarantee of saving the life of a patient with severe hypothyroidism.

Primary hypothyroidism presenting as neuropsychiatric symptoms and pituitary enlargement in a young woman: illustrative case.

Pituitary adenomas are the most common cause of pituitary enlargement and can potentially warrant surgical intervention. However, there are physiological causes of pituitary enlargement that can be reversed with hormone replacement alone. A 29-year-old female presented with acute onset paranoia to the psychiatry department. A computed tomography scan of the head revealed a 2.3 cm sellar mass with confirmation on magnetic resonance imaging. Testing showed a markedly elevated thyroid-stimulating hormone 1,600 µIU/mL (0.470-4.200 µIU/mL), suggesting pituitary hyperplasia. Treatment with levothyroxine replacement resulted in marked improvement in symptoms and resolution of pituitary hyperplasia on four month follow up. This rare presentation of severe primary hypothyroidism highlights the importance of evaluating for physiological causes of pituitary enlargement.

Severe primary hypothyroidism presenting as polymorphic ventricular tachycardia

Severe primary hypothyroidism presenting as polymorphic ventricular tachycardia

A massive ovarian cyst masquerading as malignancy in unrecognised primary hypothyroidism

We report here probably a huge ovarian cyst of size 7.9x16.4x23 cms which regressed on thyroxine therapy with severe autoimmune primary hypothyroidism in a young woman. It is necessary to consider hypothyroidism and other endocrine disorders in the differential diagnosis of adult patients with ovarian multiple cyst formation in order to prevent inadvertent ovarian surgery.

Multisystem involvement in severe primary hypothyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Atrophic autoimmune thyroiditis complicated with systemic lupus erythematosus.

Atrophic autoimmune thyroiditis (AAT) is a type of autoimmune thyroiditis that causes hypothyroidism without thyroid enlargement. AAT is distinguished from Hashimoto's disease (HD) by the absence of thyroid enlargement. AAT is rare in children and clinically characterised by severe primary hypothyroidism. Autoimmune thyroiditis, especially HD, is commonly complicated with systemic lupus erythematosus (SLE). Here, we reported the patient with AAT as the initial presentation of SLE complicated with generalised myxoedema, whose presentation was a diagnostic challenge. This patient illustrates the importance of the early recognition of an atypical presentation of SLE patients with autoimmune thyroiditis. It is possible that similar cases have existed in the past but have been overlooked as HD. A large-scale study is necessary to clarify the reality of AAT in SLE.

Pituitary Hyperplasia secondary to Severe Primary Hypothyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pattern Recognition versus Pathogenesis: Electrolytes in a Patient with Adrenal Insufficiency.

Pattern Recognition versus Pathogenesis: Electrolytes in a Patient with Adrenal Insufficiency.

Irisin as a Potential Biomarker Associated with Myocardial Injuries in Patients with Severe Hypothyroidism.

Objective Irisin, a novel myokine, has recently been considered to produce a cardioprotective effect. Potential biomarkers for myocardial injuries in patients with severe hypothyroidism have yet to be identified. We aimed to investigate whether serum irisin may serve as a promising biomarker for early detecting the myocardial injuries in patients with severe hypothyroidism. Methods This cross-sectional study comprised 25 newly diagnosed drug-naive patients with severe primary hypothyroidism and 17 age- and sex-matched healthy controls. Circulating irisin levels and cardiac magnetic resonance (CMR) were evaluated in each participant. Left ventricular (LV) myocardial injuries were detected by CMR-based T1 mapping technique using a modified look-locker inversion recovery (MOLLI) sequence, which is quantified as native T1 values. Results Compared with healthy controls, the severe hypothyroidism group had significantly lower levels of serum irisin, especially those with pericardial effusion (P < 0.05). The severe hypothyroidism subjects exhibited lower peak filling rates (PFRs) and higher native myocardial T1 values than controls (P < 0.05). Additionally, the ROC analysis displayed that the sensitivity and specificity of serum irisin for diagnosing pericardial effusion in patients with severe hypothyroidism were 73.3% and 100.0%, respectively. The AUC was 0.920 (0.861–1.000) (P < 0.001). The cutoff value was 36.94 ng/mL. Moreover, the results in subgroup analysis revealed that the native T1 values of the low-irisin group were significantly higher than that of the high-irisin group (P < 0.05). According to multivariate linear regression analysis, serum irisin concentrations were negatively and independently correlated with native myocardial T1 values after adjustment for age, sex, and other conventional confounding factors (β = −1.473, P < 0.05). Conclusions Irisin may be a potential biomarker for predicting myocardial injuries in patients with severe hypothyroidism.

Abstract #1004330: Severe Primary Hypothyroidism Causing Sudden Cardiac Arrest in a Male: A Case Report

Abstract #1004330: Severe Primary Hypothyroidism Causing Sudden Cardiac Arrest in a Male: A Case Report

Immune Check Point Inhibitors Triggering Non Autoimmune Polyendocrinopathy

The superlative therapeutic response of cancer immunotherapy is activation of the immune system against cancer cells. Currently, one of the most considered immune system enhancer are the immunomodulatory antibodies well known as checkpoint inhibitor therapy. Among this type of treatment, programed cell death-1 receptor blocker, is one of the most sought-after therapies on demand now a day. Notwithstanding the important clinical benefits of this therapeutic modality, serial autoimmune adverse effects and variety of atypical presentations of life-threatening endocrinopathies are expected to occur.We present a case of a 78-year-old man with dyslipidemia and lung CA who was referred to our clinic after developing electrolyte disturbances with associated dizziness and fatigue one month after Pembrolizumab therapy initiation. Physical exam was unremarkable. Laboratory data was consistent with mild hyponatremia, hyperkalemia and adequate fasting blood sugar levels. Aldosterone levels were extremely low, ACTH levels were extremely high with inappropriate low total cortisol response and negative 21-Hydroxylase antibodies. Diagnosis of primary adrenal insufficiency was established and Fludrocortisone 0.05 mg PO daily therapy was started with further resolution of hyponatremia and initial symptoms. In addition, concurrent primary hyperthyroidism along with thyroid RAIU-Scan results were consistent with thyroiditis, but TSI and TPO’s antibody levels were unexpectedly negative. Eventually, a suspicious thyroid nodule was identified requiring biopsy. Initial FNA results showed a follicular lesion of undetermined significance followed by a benign finding when repeated after six months. During follow up, patient’s primary hyperthyroidism converted to severe primary hypothyroidism without any intervention for her prior hyperthyroidism. Patient’s TPO’s levels remain undetectable and his current status is post-thyroiditis with residual primary hypothyroidism. Primary adrenal insufficiency also persist and its antibodies have not yet been identified either.It is known that autoimmunity can predispose to the development of primary adrenal and thyroid disorders in patients undergoing PD-1 receptor blockers therapy against cancer. Both disorders are increasingly recognized and reported as one of the most common adverse effects presenting in patients treated with these agents. However, to our knowledge, cases of non-immune related adverse effects are barely documented. This case of uncommon endocrine manifestations related to checkpoint inhibitors therapy is meritorious of being reported since it should raise awareness in the medical community for prompt identification of signs and symptoms, as well as to offer adequate management, accurate treatment and provide a better standard of care.

Pituitary Hyperplasia Secondary to Primary Hypothyroidism Mimicking a Macroadenoma With Optical Chiasm Compression

Background: A long term untreated primary hypothyroidism can stimulate thyrotropes proliferation, leading to pituitary hyperplasia. This condition is known as pituitary hyperplasia secondary to primary hypothyroidism (PHPH). It is a rare condition that mimics pituitary adenoma and can achieve large proportions with optic chiasm compression. A misdiagnosis may be catastrophic, and a pituitary resection wrongly performed. Clinical Case: A 25-year-old woman with a medical history of delayed neuro psychomotor development and epilepsy due to congenital CNS malformation had a Brain MRI performed for epilepsy follow-up three years earlier. At that time, neuroimaging had shown a pituitary enlargement, and laboratory data were diagnostic of severe primary hypothyroidism with TSH of 290.6 uUI/mL (normal range 0.4 to 4.5 uUI/mL) and T4L <0.23 ng/dL (normal range: 0.9 to 1.8 ng/dL). She then had received a 75 mcg levothyroxine prescription. However, the patient missed medical follow-up and returned three years later, when sella turcica MRI showed a 0.9x1.0x1,4 cm pituitary lesion, consistent with a macroadenoma with suprasellar extent near the optic chiasm. Because of the cognitive impairment, the patient was not able to complete the visual field test. Neurology service referred the patient to endocrinology evaluation for surgical treatment. Hypothyroidism was still uncontrolled with TSH 157.1 uUI/mL and T4L 0.28 ng/dL. We had adjusted the levothyroxine dose to 125 mcg and advised adherence. Subsequent thyroid function tests had shown TSH 6.91 uUI/mL and T4L 1.15 ng/dL. After thyroid function stabilization, the patient performed a new sella turcica MRI, which had not evidenced pituitary lesion. Pituitary hyperplasia secondary to primary hypothyroidism was her final diagnosis. Conclusion: This case report illustrates the importance of the correct diagnosis and treatment of PHPH. Levothyroxine replacement, with TSH normalization, reverses the gland hyperplasia within 2 to 4 months.

Severe primary hypothyroidism in an apparently asymptomatic 19-year-old woman: a case report

BackgroundHypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism.Case presentationWe report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient’s insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment.ConclusionThere is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.

Thyrotropin N-glycosylation and Glycan Composition in Severe Primary Hypothyroidism.

ContextIn severe primary hypothyroidism (sPH), the serum thyrotropin (TSH) levels are elevated with an increased degree of sialylation. The circulating TSH comprises 2 different TSH glycoforms: TSHdi with 2 and TSHtri with 3 N-glycans and methods have developed to determine their contents of anionic monosaccharides (AMS), that is, sialic acid (SA) and sulfonated N-acetylglactosamine (SU) residues.ObjectiveCharacterize N-glycosylation and glycan composition of circulating TSH molecules and determine the effects during levothyroxine treatment in patients with sPH.MethodsSerum samples were obtained from 25 patients with sPH, from 159 euthyroid individuals, and from 12 women during treatment with levothyroxine for sPH. Degrees of N-glycosylation and concentrations of TSHdi and TSHtri as well as their contents of AMS, SA, and SU residues were determined.ResultsThe circulating TSH molecules in sPH patients had lower degrees of N-glycosylation, higher degrees of sialylation, and lower degrees of sulfonation than in euthyroid individuals. Levothyroxin restored sialylation and sulfonation of the glycans already at low free thyroxine (FT4) levels, while degree of N-glycosylation was not restored until the FT4 levels were normal.ConclusionsThe majority of TSH molecules in severe primary hypothyroidism were less N- glycosylated, more sialylated, and less sulfonated compared with euthyroid individuals. This glycan pattern favors a prolonged half-life in the circulation combined with lower in vitro biopotency at the target cells. During levothyroxine treatment of sPH patients, the sialylation and sulfonation of glycans were restored already at low FT4 levels, while N-glycosylation of TSH was not restored until the FT4 levels were normal.

The Myxedema coma in children and adolescents: A rare endocrine emergency - Personal experience and review of literature.

Decompensated hypothyroidism, formerly known as myxedema coma, represents the most extreme clinical expression of severe primary or secondary hypothyroidism in which patients exhibit multiple organ abnormalities and progressive mental deterioration. The exact incidence of myxedema coma in adults is not known, but some authors have estimated that is approximately 0.22 per 100.0000 per year in the western world. Myxedema coma is more common in females and during winter months. The diagnosis of myxedema coma is primarily clinical with supportive evidence of the abnormal thyroid function tests. Clinical features vary depending on a several factors including the age of onset and the severity of the disease. In the majority of patients (95%), the cause of underlying hypothyroidism is autoimmunity, i.e., Hashimoto thyroiditis or congenital abnormalities. Rarely it occurs in secondary (central) hypothyroidism, due to thyrotropin deficiency related to pituitary disease, or pituitary-thyroid damage due to iron overload. Treatment consists of thyroid hormone replacement, correction of electrolyte disturbances, passive rewarming, treatment of infections, respiratory and hemodynamic support, and administration of stress-dose glucocorticoids. Prognosis seems to be better in children and adolescents compared to adults. The present review reports personal experience and the literature data on 13 patients. (www.actabiomedica.it)

Proteinuria in Severe Hypothyroidism: A Prospective Study.

Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown. This study explores the effect of thyroid hormone replacement therapy on eGFR and 24-hour urine protein excretion in patients with severe primary hypothyroidism. This study was a prospective, observational cohort study in adults with severe primary hypothyroidism (serum thyrotropin [TSH] > 50 µIU/mL). Individuals with preexisting or past kidney disease, kidney or urinary tract abnormalities, calculi or surgery, diabetes mellitus, or hypertension were excluded. The participants received thyroid hormone replacement therapy. Thyroid functions, eGFR, 24-hour urine protein excretion, and biochemical parameters were measured at baseline and 3 months. This study took place at a single center, a tertiary care referral and teaching hospital. Of 44 enrolled participants, 43 completed 3 months of follow-up. At 3 months, serum TSH levels decreased and thyroxine levels increased (P < .001 for both). Significant increases in eGFR (mean difference, 18.25 ± 19.49 mL/min/1.73 m2; 95% CI, 12.25 to 24.25, P < .001) and declines in 24-hour urine protein excretion (mean difference, -68.39 ± 125.89 mg/day; 95% CI, -107.14 to -29.65, P = .001) were observed. Serum cholesterol and low-density lipoprotein levels also significantly decreased (P < .001). Thyroid hormone replacement therapy in patients with severe primary hypothyroidism improves eGFR and decreases 24-hour urine protein excretion, thereby suggesting reversible alterations.

Clinical and Biochemical Characteristics of Severe Hypothyroidism Due to Autoimmune Thyroiditis in Children.

Introduction: In the majority of countries, autoimmune thyroiditis is the main cause of acquired hypothyroidism in children. Typically, the natural course of the disease is initially insidious and the diagnosis is incidental. There are some children who develop severe hypothyroidism without a proper diagnosis. The aim of the study was to analyze the clinical and biochemical profiles of children with severe primary hypothyroidism due to autoimmune thyroiditis.Materials and Methods: We analyzed the records of 354 patients diagnosed between 2009 and 2019 with autoimmune thyroiditis. Only patients with TSH above 100 μIU/mL, associated with decreased free thyroxine and the presence of antithyroid antibodies, were enrolled in the study. The analysis encompassed clinical symptoms, thyroid and biochemical status, bone age, and imaging.Results: Twenty-six children were enrolled in the study. The mean age at diagnosis was 10.26 ± 3.3 years, with a female preponderance of 1.8:1. The most frequent symptom was growth impairment (77%) and weight gain (58%). Goiters were present in 42% of patients. Less common findings were pituitary hypertrophy (four patients) and hypertrichosis (three patients). Median values at the time of diagnosis were TSH 454.3 uIU/ml (295.0–879.4), anti-TPO antibodies 1,090 IU/ml, and anti-Tg antibodies 195 IU/ml. Anti-TSHR ab were evaluated only in six out of the 26 patients. The characteristic biochemical profile was correlated with the grade of hypothyroidism, and the strongest correlations were found with CBC parameters, lipid profile, aminotransferases, and creatine.Conclusion: In children with severe hypothyroidism, the most sensitive symptoms are growth arrest and weight gain despite the fact that, in some children, the auxological parameters at presentation could be within normal values for the population. The specific biochemical profile closely correlates to the severity of thyroid hormone deficiency and involves mostly erythropoiesis, liver function, and kidney function. Pituitary enlargement should be considered in each child with severe hypothyroidism. It is necessary to conduct prospective studies evaluating the actual frequency of anti-TSHR antibodies and pituitary enlargement in children with extremely high TSH, especially those presenting without goiters.

SUN-277 Pituitary Hyperplasia Due to Severe Primary Hypothyroidism: An Uncommon Manifestation of a Common Disease

Background Pituitary hyperplasia (PH) is a non-neoplastic increase in one or more cell subtype of the adenohypophysis. It is physiologically seen in pregnancy from resultant lactotroph hyperplasia and pathologically in organ dysfunctions that lead to loss of negative feedback on hypothalamus like primary hypothyroidism and primary adrenal insufficiency. Although primary hypothyroidism is common, PH is an under-recognized consequence of long-standing hypothyroidism. Case Description A 26-year-old female with class 3 obesity, type 2 diabetes mellitus, and primary hypothyroidism on replacement presented for evaluation of secondary amenorrhea. Two months prior to presentation, she underwent a brain MRI for new-onset headache which revealed diffusely enhancing homogenous pituitary tissue measuring 2.3 cm with upward lifting of the optic chiasm. Serum prolactin was elevated at 86.2 ng/ml (2.8-26 ng/ml). This was presumed to be secondary to a prolactinoma and cabergoline was started by the referring provider. Subsequent workup revealed elevated thyroid-stimulating hormone (TSH) at 494.11 mU/L (0.30- 4.00 mU/L) and a low free thyroxine (FT4) of 0.2 ng/dl (0.8-1.7 ng/dl). Other pituitary hormones were within normal limits. The visual field examination was normal. It was noted she had a persistently elevated TSH over the past five years. On further questioning, the patient ran out of levothyroxine replacement 6 months ago and had been generally non-adherent to therapy for years due to nausea. Improved medication adherence resulted in the normalization of prolactin and reduction in TSH level. Repeat MRI 2 months later revealed a reduction in her pituitary hyperplasia to 2.1 cm. Discussion In severe primary hypothyroidism, there is loss of negative feedback to the hypothalamus due to low circulating FT4 and triiodothyronine (T3) concentrations. As a result, there is stimulation of thyrotropin-releasing hormone (TRH) which promotes thyrotroph hyperplasia. A strong correlation exists between TSH concentration and the degree of pituitary hyperplasia. The typical MRI finding is a diffusely enhancing homogenous pituitary mass. Despite optic chiasm contact, physiologic pituitary hyperplasia rarely causes visual field defects. High concentrations of TRH stimulates prolactin release with resultant mild hyperprolactinemia. Although PH is reversible with therapy, rare cases with subsequent development of panhypopituitarism while on therapy have been reported in the setting of longstanding hypothyroidism. Very rarely, chronically untreated primary hypothyroidism can stimulate the growth of a thyrotroph adenoma. Long-term biochemical and radiological monitoring is therefore recommended until resolution. This case highlights the physiologic responses manifested in severe primary hypothyroidism and the fact that these changes improve with adequate replacement.