scholarly journals The diagnosis and management of central hypothyroidism in 2018

2019 ◽  
Vol 8 (2) ◽  
pp. R44-R54 ◽  
Author(s):  
Luca Persani ◽  
Biagio Cangiano ◽  
Marco Bonomi

Central hypothyrodism (CeH) is a hypothyroid state caused by an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. Several advancements, including the recent publication of expert guidelines for CeH diagnosis and management, have been made in recent years thus increasing the clinical awareness on this condition. Here, we reviewed the recent advancements and give expert opinions on critical issues. Indeed, CeH can be the consequence of various disorders affecting either the pituitary gland or the hypothalamus. Recent data enlarged the list of candidate genes for heritable CeH and a genetic origin may be the underlying cause for CeH discovered in pediatric or even adult patients without apparent pituitary lesions. This raises the doubt that the frequency of CeH may be underestimated. CeH is most frequently diagnosed as a consequence of the biochemical assessments in patients with hypothalamic/pituitary lesions. In contrast with primary hypothyroidism, low FT4 with low/normal TSH levels are the biochemical hallmark of CeH, and adequate thyroid hormone replacement leads to the suppression of residual TSH secretion. Thus, CeH often represents a clinical challenge because physicians cannot rely on the use of the ‘reflex TSH strategy’ for screening or therapy monitoring. Nevertheless, in contrast with general assumption, the finding of normal TSH levels may indicate thyroxine under-replacement in CeH patients. The clinical management of CeH is further complicated by the combination with multiple pituitary deficiencies, as the introduction of sex steroids or GH replacements may uncover latent forms of CeH or increase the thyroxine requirements.

Author(s):  
Barbara Samec ◽  
Gaja Setnikar ◽  
Simona Gaberscek ◽  
Tomaz Kocjan

Abstract Background Contrary to patients with hypothyroidism after radioiodine (HRI) or after thyroidectomy (HTh), patients with central hypothyroidism (CH) cannot rely on thyrotropin (TSH) level to guide their treatment with L-thyroxine (L-T4). Consequently, they are at constant risk of under- or overtreatment. We aimed to establish the adequacy of L-T4 treatment in patients with CH in our cohort. Methods Consecutive patients with CH on L-T4 treatment were compared with patients adequately treated for HRI or HTh. Levels of free thyroxine (fT4) and free triiodothyronine (fT3) were evaluated and the fT4/fT3 ratio was calculated. Results Forty patients with CH, 136 patients with HRI and 43 patients with HTh were included in this study. Patients with HRI were significantly younger than patients with HTh and CH (p<0.001 for both). Levels of fT4 were significantly lower in CH than in adequately treated patients with HRI and HTh (median (range), 15.6 (12.7–21.3), 18.4 (12.2–28.8), and 18.7 (13.8–25.5) pmol/L, respectively, p<0.001 for both comparisons). Levels of fT3 did not differ significantly (p=0.521) between CH, HRI and HTh (median (range), 4.5 (2.7–5.9), 4.3 (3.2–6.2), and 4.4 (2.9–5.5) pmol/L, respectively). Accordingly, the fT4/fT3 ratio was significantly lower in the CH group than in HRI and HTh groups (median (range), 3.7 (2.5–5.2), 4.2 (1.2–7.7), and 4.4 (2.5–6.1), respectively, p<0.001 for both comparisons). Conclusions Patients with CH have lower fT4 levels and lower fT4/fT3 ratios than patients adequately treated for HRI or HTh. The cause for this difference may be the unreliable TSH levels in patients with CH.


1983 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
C. Ferrari ◽  
M. Boghen ◽  
A. Paracchi ◽  
P. Rampini ◽  
F. Raiteri ◽  
...  

Abstract. Circulating thyroglobulin antibodies (TgAb) and microsomal antibodies (MsAb) and thyroid function (total and free T4 and T3, TSH basal and after TRH) have been evaluated in 92 hyperprolactinaemic patients (82 females and 10 males; 9 with macroprolactinoma, 22 with microprolactinoma, 4 with acromegaly, 5 with organic lesions of the hypothalamus, 2 with empty sella, 2 with idiopathic hypopituitarism, 2 with primary hypothyroidism, and 46 with idiopathic hyperprolactinaemia). Thyroid function was normal in all cases except 3 with hypothalamic disease and central hypothyroidism, the 2 patients with primary hypothyroidism and 2 with thyrotoxicosis (one due to Graves' disease and one to autonomous thyroid adenoma). High titres of TgAb (≥1/1250) and/or MsAb (≥ 1/1600) were found in the subject with Graves' disease, in one acromegalic, in the 2 primary hypothyroids, and in 12 women with either adenomatous or idiopathic hyperprolactinaemia; low titres of one or both antibodies were found in 9 other euthyroid women and in the one with toxic adenoma. In a control population of 185 subjects studied with the same methods, the prevalence of TgAb and/or MsAb positive (low titres) was 3.3% in females and 2.5% in males. Diffuse thyroid hyperplasia was clinically detectable in 12 euthyroid women and in the one with Graves' disease; 3 others had been previously operated for nodular goitre with histological evidence of Hashimoto's thyroiditis (2 cases) or for a cold nodule; a single thyroid nodule was present in the woman with toxic adenoma and in one euthyroid woman. Most of these subjects also had circulating TgAb and/or MsAb, and a few had increased TSH secretion. No significant differences were found in mean thyroid hormone and TSH levels between euthyroid hyperprolactinaemic subjects and healthy controls, but TRH-stimulated TSH levels were significantly higher in thyroid antibodies positive than negative subjects. These data, in agreement with a few previous reports, suggest that autoimmune thyroid disorders (especially asymptomatic autoimmune thyroiditis) occur in hyperprolactinaemic women with a prevalence far exceeding that observed in many surveys in the general population.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5176-5176
Author(s):  
Polyxeni Delaporta ◽  
Maria Karantza ◽  
Sorina Boiu ◽  
Konstantinos Stokidis ◽  
Theoni Petropoulou ◽  
...  

Abstract Abstract 5176 Background: Disturbances of thyroid function is known to frequently occur in Thalassemia Major (TM); its types prevalence and severity vary in different cohorts. Primary hypothyroidism is caused by failure of thyroid function, while central (secondary) hypothyroidism by inefficient secretion of thyroid-stimulating hormone (TSH) due to pituitary gland dysfunction or reduced thyrotropin-releasing hormone (TRH) secretion from the hypothalamus. TSH levels in primary hypothyroidism are increased, while levels of free T4 (FT4) are decreased or within normal range. In secondary hypothyroidism FT4 levels are low and TSH levels normal or low. The main objective of this retrospective study was to assess the prevalence of central and primary hypothyroidism in a cohort of 364 Greek patients with TM (mean age 33. 0±9. 9 years, range: 1–56 years). Patients and Methods: Data from sequential laboratory evaluation on thyroid function in 364 patients with TM were retrospectively collected and analyzed. Assessment of thyroid function included measurements of TSH, T4, T3, FT4, FT3, anti-TPO, anti-TG by classical methods. Diagnostic criteria for primary hypothyroidism consisted of two consecutive measurements of low T4 or FT4 with increased TSH levels or two consecutive abnormally high levels of TSH despite normal levels of FT4, FT3, T4 and T3. The criteria for diagnosis of central hypothyroidism consisted of two consecutive measurements of low levels of T4 or FT4 with normal or low levels of TSH. In addition the age and ferritin levels at diagnosis of the hypothyroidism, as well as the type of thyroid treatment and chelation were recorded. To study the longitudinal prevalence of thyroid dysfunction, patients were stratified into 3 groups, according to the year of birth (Group A=1960–1970, 49 patients; Group B =1971–1980, 195 patients; Group C=1981–1990, 75 patients). As thyroid dysfunction increases with age, the incidence of thyroid disorders was compared between all three groups for patients ≤30years old, and for patients ≤40 years old between the groups A and B. Statistical analysis as well as BoxPlot values and regression lines presentation were performed using the STATGRAPHICS Centurion XVI. Statistical significance was set at p<0. 05. Results: A total of 364 patients (mean age 33. 0±9. 9 years, 180 females, 184 males) with TM were evaluated. Relevant data on the type and prevalence of thyroid dysfunction in all three groups of patients are summarized in table 1. Figure 1 illustrates the correlation between the age and the year of diagnosis of hypothyroidism. Comparing the data of the three age groups no significant differences in the overall prevalence of hypothryroidism was found. A significantly higher incidence of central hypothyroidism was found in group C compared to groups B and A (p=0. 00087, p=0. 0097 respectively) and higher prevalence of primary hypothyroidism in group A (for patients aged <40 years) in comparison with group B (p=0. 012). Ferritin levels at the time of diagnosis were significantly lower in group A compared to B and C and in group B compared to C (A/B p=0. 0014; B/C p=0. 0342; A/C p<0. 0001). A significant correlation (R2 =0. 47) was found between the age at diagnosis of hypothyroidism and the year of diagnosis (figure 1). Conclusions: The study demonstrated that thyroid disorders remain a frequent problem in Greek patients with TM with a trend of increasing prevalence with age and modification of the ratio of primary to secondary hypothyroidism. The increased incidence of central hypothyroidism in recent years could be attributed to an increased awareness and a more precise evaluation of this condition. The fact that ferritin levels at diagnosis were significantly higher in the younger age cohort may be suggestive that novel iron chelation modalities are more protective against iron-induced thyroid toxicity. Nevertheless, as toxicity may occur in early stages, the impact of these modalities in the incidence and severity of thyroid dysfunction may take years to be apparent. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 91 (10) ◽  
pp. 135-138
Author(s):  
N A Petunina ◽  
L V Trukhina ◽  
N S Martirosian

Central hypothyroidism is a rare cause of hypothyroidism, consequence of various disorders affecting pituitary (secondary) or hypothalamus (tertiary hypothyroidism). Difficulties in the diagnosis and management of patients are due to the nontypical clinical picture, frequent combination with impaired function of other pituitary hormones, difficulties in laboratory assessment in high TSH levels or low - normal T4 free levels. Diagnosis is based on a confirmed decrease in the level of free T4 with a low or normal level of TSH. The standard treatment for hypothyroidism of any etiology remains monotherapy with levothyroxine, which allows to restore the euthyroid state in most patients. The criterion for the effectiveness of therapy is to maintain the level of T4 free in the upper half of the reference norm interval. The article presents a modern understanding of epidemiology, pathogenesis and strategies for managing patients with central hypothyroidism.


1997 ◽  
pp. 659-663 ◽  
Author(s):  
S Corbetta ◽  
P Englaro ◽  
S Giambona ◽  
L Persani ◽  
WF Blum ◽  
...  

Leptin is the protein product of the ob gene, secreted by adipocytes. It has been suggested that it may play an important role in regulating appetite and energy expenditure. The aim of this study was to evaluate a possible interaction of thyroid hormones with the leptin system. We studied 114 adult patients (65 females and 49 males): 36 were affected with primary hypothyroidism (PH), 38 with central hypothyroidism (CH) and 40 with thyrotoxicosis (TT). Patients with CH were studied both before and after 6 months of L-thyroxine replacement therapy. Body mass index (BMI; kg/m2), thyroid function and fasting serum leptin were assessed in all patients. Since BMI has been proved to be the major influencing variable of circulating leptin levels, data were expressed as standard deviation score (SDS) calculated from 393 male and 561 female controls matched for age and BMI. No difference in SDS was recorded between males and females whatever the levels of circulating thyroid hormones. In males, no significant difference was recorded among the SDSs of PH (-0.36 +/- 1.2), TT (-0.35 +/- 1.2) and CH (0.01 +/- 1.4) patients. Females with PH had an SDSs significantly lower than TT females (-0.77 +/- 1.0 vs -0.06 +/- 1.2; P < 0.02), while no significant differences between CH (-0.34 +/- 0.7) and TT females or between CH and PH females were observed. SDS in CH patients after 6 months of L-thyroxine therapy significantly varied only in females (0.25 +/- 1.4). In conclusion, circulating thyroid hormones do not appear to play any relevant role in leptin synthesis and secretion. However, as females with either overt hypo- or hyper-thyroidism or central hypothyroidism after L-thyroxine therapy show differences in their SDSs, a subtle interaction between sex steroids and thyroid status in modulating leptin secretion, at least in women, may occur.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nordie Anne Bilbao

Abstract Pituitary stalk interruption syndrome (PSIS) is a rare condition that include congenital anatomic abnormalities of the pituitary gland and hypopituitarism. There is a wide variety of clinical presentation, with the age at presentation encompassing from neonatal period to adulthood and including one or more pituitary hormone deficiencies. In recent literature there is increasing recognition of PSIS presenting in the neonatal period, mostly involving hypoglycemia. Our patient is a full-term male infant who presented in the newborn period with hypotonia and hypothermia. He also had hypoglycemia, which was initially thought to be associated to hyperinsulinism in the context of gestational diabetes. Micropenis was noted on physical exam. As part of the study for hypotonia, serial thyroid function tests were obtained revealing central hypothyroidism. A low dose ACTH stimulation test was performed which revealed adrenal insufficiency. The patient was started on cortisol and thyroid hormone replacement. Brain MRI showed an ectopic neurohypophysis located along the floor of the hypothalamus, a small anterior pituitary gland, and a partially absent infundibulum, findings consistent with pituitary stalk interruption syndrome. The patient received testosterone injections for micropenis and is being followed for development of other pituitary hormone deficiencies. PSIS is a rare congenital condition that is increasingly recognized in neonates manifesting with signs of hypopituitarism.


1994 ◽  
Vol 22 (5) ◽  
pp. 273-277 ◽  
Author(s):  
J Taylor ◽  
B O Williams ◽  
J Frater ◽  
D J Stott ◽  
J Connell

Seven female patients (mean age 86 years) with proven biochemical primary hypothyroidism were enrolled in a single-blind randomized crossover study, of standard daily versus twice-weekly thyroxine therapy, with each phase of one month's duration. The median daily dose of thyroxine was 100 μg (range 75 – 100 μg). Serum levels of thyroid hormones and thyrotrophin were very similar during twice-weekly thyroxine therapy to those during daily therapy and there were no statistically significant differences between trough and peak serum total triiodothyronine, free thyroxine, or thyrotrophin levels or systolic time intervals during twice-weekly thyroxine. Administration of thyroxine twice-weekly to elderly patients with primary hypothyroidism gives effective biochemical thyroid hormone replacement, with no evidence from the systolic time intervals of tissue thyrotoxicosis at expected peak thyroid hormone concentrations. Supervised twice-weekly thyroxine should be considered in patients with primary hypothyroidism who comply poorly with daily dosing.


2005 ◽  
Vol 49 (3) ◽  
pp. 468-472 ◽  
Author(s):  
Luiz Augusto Casulari ◽  
Fábio Celotti ◽  
Luciana A. Naves ◽  
Lucília Domingues ◽  
Carla Papadia

Long term use of high doses of estrogen and the presence of chronic hyperprolactinemia may, at least in the rat, provoke lesions in the tuberoinfundibular dopaminergic (TIDA) neurons responsible for the control of prolactin (Prl) secretion. This occurrence, which is not yet well documented in humans, may have taken place in a patient on chronic oral hormonal contraceptive (OC) treatment who was seen for primary hypothyroidism, hyperprolactinemia and a pituitary mass. After thyroid hormone replacement, OC withdrawn and bromocriptine treatment, this patient could not maintain normal Prl levels, unless continuously treated with a dopaminergic agonist even when MRI was indicative of a normal situation. Function of TIDA neurons was investigated by TRH test (200µg IV) performed before and after treatment with 25mg carbidopa plus 250mg L-dopa every 4 hours for one day. Basal TSH was normal (3.9µU/mL) whereas basal Prl was high (67.5 ng/mL); both TSH and Prl levels appropriately increased after TRH: peaks 31.8µU/mL and 157.8 ng/mL, respectively. After treatment with carbidopa/L-dopa, basal TSH (1.6µU/mL) and Prl (34ng/mL) decreased and the response to TRH was partially blocked (10.3µU/mL and 61ng/mL, respectively). In spite of a normal response, we discuss the possibility that the persistence of hyperprolactinemia is due to lesion of the TIDA neurons produced by the long term use of high doses of estrogens and by the presence of chronic hyperprolactinemia.


2011 ◽  
Vol 55 (4) ◽  
pp. 291-293 ◽  
Author(s):  
Bashir Ahmad Laway ◽  
Syed Tufail ◽  
Mir Iftikhar Bashir ◽  
Mohd Ashraf Ganie ◽  
Abdul Hamid Zargar

Premature ovarian failure has an overall prevalence of 0.3% to 0.9% in general population. If fertility is a concern, treatment usually consists of estrogen therapy as hormone replacement and oocyte donation. Spontaneous pregnancy in affected women is uncommon. We report a case of a 34-year old woman, who had premature ovarian failure and primary hypothyroidism, and conceived spontaneously eleven years after the development of premature ovarian failure and correction of hypothyroidism.


Sign in / Sign up

Export Citation Format

Share Document