Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

Treatment of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

"Micromegaly": Acromegaly with apparently normal GH, an entity on its own?

A small proportion of the patients with acromegaly present with apparently normal basal GH levels and suppressible GH levels despite increased IGF-1 levels, a pattern called micromegaly by some authors. Whether this pattern represents a distinct entity or is just an expression of acromegaly in its early stages is still a matter of debate. Nevertheless, these patients have some peculiar characteristics such as being more likely older and male, mostly harbour microadenomas or small macroadenomas, and have lower IGF-1 and postglucose GH levels. Even though, the frequency and severity of clinical signs and comorbidities are similar to those of patients with classic acromegaly. In conclusion, micromegaly seems to be a distinct clinical entity with a different biological behavior characterized by a low GH output.

Subclinical central hypothyroidism in patients with hypothalamic-pituitary disease: does it exist?

Central hypothyroidism (CH) is characterized by decreased thyroid hormone production due to insufficient stimulation of an otherwise normal thyroid gland by TSH. In patients with established hypothalamic-pituitary disease, a low FT4 concentration is considered highly specific, although poorly sensitive, for the diagnosis of CH. That would be comparable to diagnosing primary hypothyroidism in patients at risk only when serum FT4 concentrations are below the reference range, missing all patients with subclinical primary hypothyroidism and preventing proper therapy in patients in which thyroxine replacement is clearly beneficial. Cardiac time intervals, especially the isovolumic contraction time (ICT), have been considered the gold standard of peripheral thyroid hormone action. Using Doppler echocardiography, we have previously shown a very high proportion of prolonged ICT in patients with hypothalamic-pituitary disease and serum FT4 levels indistinguishable from controls. As ICT decreased/normalized after thyroxine-induced increases in FT4 concentrations within the normal reference range, prolonged ICT was considered a bona fide diagnostic biomarker of subclinical CH. Those findings challenge the usual interpretation that FT4 concentrations in the mid-reference range exclude hypothyroidism in patients with hypothalamic-pituitary disease. Rather, subclinical central hypothyroidism, a state analogous to subclinical primary hypothyroidism, seems to be frequent in patients with hypothalamic-pituitary disease and normal FT4 levels. They also challenge the notion that thyroid function is usually the least or the last affected in acquired hypopituitarism. The relevance of Doppler echocardiography to correctly diagnose and monitor replacement therapy in both clinical and subclinical forms of CH should improve quality of life and decrease cardiovascular risk, as already demonstrated in patients with clinical and subclinical primary hypothyroidism.

Pompe disease misdiagnosed as polymyositis.

Late-onset Pompe disease manifests predominantly in the proximal lower limbs and may be mistaken for an inflammatory myopathy. A 46-year-old man with acromegaly had an 8-year history of progressive weakness. His myopathy was initially attributed to the acromegaly, but severe progression prompted a muscle biopsy, which suggested an inflammatory myopathy. However, his weakness progressed despite treatment for polymyositis. His muscle ultrasound scan pattern was more suggestive of Pompe disease than polymyositis, and Pompe disease was confirmed by genetic and enzymatic testing. Patients with apparent polymyositis, which persists despite treatment, require reconsideration of the diagnosis, with particular attention to treatable genetic causes.

Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

Treatment of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

Does Postpartum Hypopituitarism Influence the Craniofacial Pattern? A Case-Control Study with Sheehan's Syndrome Patients

This study aimed to assess the craniofacial morphologic aspects of Sheehan's syndrome (SHS) patients.An observational study was performed with 19 women diagnosed with SHS and 19 controls matched by age and sex. Lateral cephalometric radiographs were obtained, and 30 linear and angular measurements were analyzed using the Radiocef Studio 2 software. The mean age of patients was 65.47 ± 10.19 years. The main findings were propositioned maxilla (52.63 %) and mandible (52.63 %) relative to the cranial base, mandibular prognathism in 73.68 %, deep growth pattern in 42.1 %, increased mandibular plane in 36.84 %, and reduction in anterior facial height. The SHS group showed statistically significant differences in SNB (p=0.026), N-Me (p=0.006), soft palate length (p=0.011), and Ena-Me (p<0.001) in comparison with controls. The standard deviation score analysis revealed altered values in relation to total maxillary and mandibular lengths. SHS showed altered craniofacial morphology, characterized by maxillo- mandibular prognathism, brachyfacial type, increased mandibular plane, and reduction in soft palate length. This study reports novel findings in SHS.

Este estudio tuvo como objetivo evaluar los aspectos morfológicos craneofaciales de los pacientes con síndrome de Sheehan (SHS). Se realizó un estudio observacional con 19 mujeres diagnosticadas con SHS y 19 controles asociados por edad y sexo. Se obtuvieron radiografías cefalométricas laterales y se analizaron 30 medidas lineales y angulares mediante el software Radiocef Studio 2. La edad media de los pacientes fue de 65,47 ± 10,19 años. Los principales hallazgos fueron proposición maxilar (52,63 %) y mandíbula (52,63 %) con respecto a la base del cráneo, prognatismo mandibular en 73,68 %, patrón de crecimiento profundo en 42,1 %, aumento del plano mandibular en 36,84 % y reducción de la altura facial anterior. El grupo SHS mostró diferencias estadísticamente significativas en SNB (p=0,026), N-Me (p=0,006), longitud del paladar blando (p=0,011) y Ena-Me (p<0,001) en comparación con los controles. El análisis de la puntuación de la desviación estándar reveló valores alterados en relación con las longitudes maxilares y mandibulares totales. El SHS mostró una morfología craneofacial alterada, caracterizada por prognatismo maxilomandibular, tipo braquifacial, aumento del plano mandibular y reducción de la longitud del velo del paladar. Este estudio informa hallazgos novedosos en SHS.

Impact of the COVID-19 pandemic in the treatment of patients with acromegaly in a tertiary center: a wake-up call on the importance of telemedicine

ABSTRACT Objective: The COVID-19 pandemic has profoundly disrupted health care worldwide. We aimed to evaluate the impact of the first COVID-19 wave on the treatment of our patients with acromegaly. Subjects and methods: A standard questionnaire was systematically applied to all patients and included questions on general health status, whether all laboratory workup had been done, common signs and symptoms of acromegaly, treatment adherence, and previous COVID-19 symptoms and diagnosis. Results: We attempted to contact 136 patients with acromegaly at regular follow-up at our institution and contacted 101 of them successfully. In all, 37% of the patients reported symptoms of acromegaly, which was more common among women. A total of 27 patients were lost to follow-up (including 19 who interrupted treatment during the pandemic) mainly for fear of becoming infected by the SARS-CoV-2. Of these, 24 resumed follow-up after our contact. Conclusions: The current COVID-19 pandemic has strongly impacted the follow-up of patients with acromegaly. Telemedicine can be an important tool to maintain regular treatment in the current or future pandemics.

Impact of the COVID-19 pandemic in the treatment of patients with acromegaly in a tertiary center: a wake-up call on the importance of telemedicine.

Introduction: The COVID-19 pandemic has profoundly disrupted health care worldwide. We aimed to evaluate the impact of the first COVID-19 wave on the treatment of our patients with acromegaly. Subjects and methods: A standard questionnaire was systematically applied to all patients and included questions on general health status, whether all laboratory workup had been done, common signs and symptoms of acromegaly, treatment adherence, and previous COVID-19 symptoms and diagnosis. Results: We attempted to contact 136 patients with acromegaly at regular follow-up at our institution and contacted 101 of them successfully. In all, 37% of the patients reported symptoms of acromegaly, which was more common among women. A total of 27 patients were lost to follow-up (including 19 who interrupted treatment during the pandemic) mainly for fear of becoming infected by the SARS-CoV-2. Of these, 24 resumed follow-up after our contact. Conclusion: The current COVID-19 pandemic has strongly impacted the follow-up of patients with acromegaly. Telemedicine can be an important tool to maintain regular treatment in the current or future pandemics.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism.

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Giant Prolactinoma Causing Hydrocephalus and Intracranial Hypertension as First Manifestations of Multiple Endocrine Neoplasia Type 1.

Context: Overall, giant prolactinomas are rare tumors (4%), especially those larger than 60 mm (1%). Despite the predominance of macroadenoma documented in multiple endocrine neoplasia type 1 (MEN1)-related prolactinoma, only three giant prolactinoma cases were described so far (size > 40 mm and prolactin > 1,000 ng/mL). None of them was larger than 60 mm or presented hydrocephalus or intracranial hypertension (ICH) as initial manifestation of MEN1. Case Description: A 21-years-old man presented with ICH as the first clinical manifestation of MEN1. He harbored a MEN1 germline mutation but refused periodic vigilance after normal hormonal screening at age 14 years. During investigation, magnetic resonance imaging (MRI) of the skull showed an expansive sellar/parasellar lesion (75 × 44 × 36 mm) with moderate to severe supratentorial obstructive hydrocephalus and an extremely high serum prolactin (PRL) of 10,800 ng/mL, without combined hypersecretion of other pituitary hormones. He was diagnosed with giant prolactinoma, and cabergoline was initiated. The patient evolved with early improvement of clinical complaints for hydrocephalus and ICH and PRL reached normal values (11 ng/mL) in association with significant tumoral shrinkage after 18 months on cabergoline. After 2 months of cabergoline, cerebrospinal fluid leakage was diagnosed and corrective surgery was provided. The mean dose of cabergoline was 3 mg/week throughout treatment. Conclusion: We reported the first case with hydrocephalus and ICH as the initial clinical manifestation of a giant prolactinoma in MEN1. From our knowledge, this is the largest MEN1-related prolactinoma reported so far. Notably, all four MEN1-related giant prolactinomas cases reported were younger than 21 years strengthening the importance to routine MEN1 genetic testing for prolactinoma in this age group. Also, they all had initial effective response with dopamine agonist ensuring this drug as first-line treatment for MEN1-related giant prolactinoma. However, the scarce number of treated patients and progression of cabergoline resistance in two of them suggest strict surveillance.

Development and validation of a method for the analysis of pyrethroid residues in fish using GC-MS.

The presence of the pyrethroids residues in different samples and the impact on human health is an increasing concern due to their widespread use. So, a method to determine eighteen pyrethroids in fish samples using a modified QuEChERS was developed. The clean-up procedure was performed by freezing samples overnight followed by dispersive solid phase extraction. The combination of C18, PSA and Z-Sep+ was optimized using a mixture design approach and samples were analysed using gas chromatography mass spectrometry. The method was validated using trahira samples and a scope extension was performed for tilapia and tainha. Recoveries were within 63-129%, relative standard deviation was ≤21.5% and the quantification limits were 5 µg kg-1 or 10 µg kg-1. The applicability of the method was assessed by analysis of fourteen real samples, in which residues were detected in four samples. Such detections demonstrate the importance of this sensitive method.

Levothyroxine Replacement Improves Oxidative Status in Primary Hypothyroidism.

Objective: Although hypothyroidism has been linked to oxidative stress, data regarding the relationship between thyroid hormone levels and oxidative stress is still inconsistent. This study was designed to evaluate the effect of levothyroxine replacement on oxidative stress in women with primary hypothyroidism. Design: A total of 25 female patients with primary hypothyroidism were included. Oxidative stress markers were measured before and after levothyroxine replacement treatment in all patients. Methods: Oxidative stress was evaluated through the measurement of oxidants (thiobarbituric acid reactive substances [TBARS] and nitrite/nitrate levels), and antioxidants (superoxide dismutase and catalase activity). Results: Antioxidant catalase activity (63.77 ± 23.8 vs. 50.12 ±12.75 atv/min; p = 0.03) was significantly increased and the levels of TBARS (3.02 ± 0.86 vs. 3.55 ± 0.87 µM; p = 0.03) were significantly decreased in the state of euthyroidism after levothyroxine replacement compared to the hypothyroidism before levothyroxine treatment. No significant change in neither nitrite/nitrate concentration (p = 0.18) nor in superoxide dismutase activity (p = 0.93) after L-T4 adjustment was found. Conclusions: Our data demonstrate that levothyroxine replacement improved oxidative status in patients with primary hypothyroidism, indexed by the significantly decreased levels of malonaldehyde (MDA) and increased catalase (CAT) activity.

Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism.

Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.