HELLP syndrome, also known as the syndrome of hemolysis, elevated liver enzymes, and low platelets, represents a severe pregnancy complication typically associated with hypertension. It is associated with increased risks of adverse complications for both mother and fetus. HELLP occurs in 0.2–0.8% of pregnancies, and, in 70–80% of cases, it coexists with preeclampsia (PE). Both of these conditions show a familial tendency. A woman with a history of HELLP pregnancy is at high risk for developing this entity in subsequent pregnancies. We cannot nominate a single worldwide genetic cause for the increased risk of HELLP. Combinations of multiple gene variants, each with a moderate risk, with concurrent maternal and environmental factors are thought to be the etiological mechanisms. This review highlights the significant role of understanding the underlying pathophysiological mechanism of HELLP syndrome. A better knowledge of the disease’s course supports early detection, an accurate diagnosis, and proper management of this life-threatening condition.

Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017–June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5–10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40–72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic–lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory.

Postpartum depression (PPD) is a disabling condition that has recently shown an increase in prevalence, becoming an essential public health problem. This study is a qualitative review summarizing the most frequent risk factors associated with PPD, evaluating molecular aspects of PPD and current approaches to detect and prevent PPD. The most prevalent risk factors were detected in the areas of economic and social factors, obstetrical history, lifestyle, and history of mental illness. Research on the genetic basis for PPD has taken place in recent years to identify the genes responsible for establishing targeted therapeutic methods and understanding its pathogenesis. The most frequently studied candidate gene was the serotonin transporter gene (SERT) associated with PPD. Among biological studies, antidepressants and psychological interventions provided the most evidence of successful intervention. The obstetrician can serve an essential role in screening for and treating PPD. Postpartum women with risk factors should be screened using the Edinburgh Postnatal Depression Scale (EPDS), but, at the moment, there are no prevention programs in Europe. In conclusion, data from this review increase concerns among this vulnerable population and can be used to design a screening tool for high-risk pregnant women and create a prevention program.

Peutz‑Jeghers syndrome (PJS), a rare autosomal dominant serine/threonine kinase 11 (STK11)/ liver kinase B1 (LKB1) gene‑related genodermatosis, is characterized by oral hyperpigmentation (OHP); multiple gastro‑intestinal mucosal benign hamartomatous polyps causing local bleeding, occlusion, intussusception, post‑resection small bowel syndrome, associated increased risk of small intestinal cancer (incidence during the third decade); and 76% cumulative higher risk than the global population of developing non‑gastrointestinal tumors (female predominance) including ovarian/testicular neoplasia, pancreatic and gynecologic (breast, uterus, ovarian) cancers. Suggestive PJS‑associated OHP requires STK11 genetic testing. Abdominal pain in an OHP patient may be related to PJS‑associated polyps. Other features include focal depigmentation followed by hyperpigmentation, and xeroderma pigmentosum‑like lesions. The severity of the dermatological findings is correlated with gastrointestinal polyps. The STK11 gene is linked to reserve of primordial follicles, polycystic ovary syndrome, female fertility, and spermatogenesis. PJS is associated with 2 types of ovarian sex‑cord stroma tumors (SCSTs): annular tubules (SCTATs) and pure Sertoli cell tumors. SCSTs accounts for 8% of ovarian cancer and SCTATs represents 2% of SCST, which may be associated with the overproduction of progesterone. PJS‑SCTAT vs. non‑PJS‑SCTAT reveals bilateral/multifocal, small tumors with a benign behavior vs. a unique ovarian, large tumor with increased malignant/metastasis risk. Male precocious puberty is due to large cell calcifying Sertoli cell tumors (LCCSCTs). Notably, 30‑40% of LCCSCTs are caused by PJS or Carney complex. PJS‑LCCSCT is not aggressive, but it may be bilateral/multifocal, with the ultrasound hallmark being micro‑calcifications. Testicular, intra‑tubular large cell hyalinizing Sertoli cell tumor is the second testicle neoplasia in PJS. The skin and mucosal lesions are useful markers of PJS, assisting with the early identification of hamartomatouspolyps and initiation of serial surveillance of ovarian, or testicular neoplasia.

Thyroid hormones are required for the physiological growth and maintenance of hair follicles. We aim to study the thyroid profile of patients with alopecia. This is a narrative review. PubMed literature was searched from 2013 to 2022. We followed different types of alopecia: alopecia areata (AA), androgenic alopecia in males and females, telogen effluvium (TE), frontal fibrosing alopecia (FFA), lichen planopilaris, and alopecia neoplastica (AN). AA shares a common autoimmune background with autoimmune thyroid diseases, either sporadic or belonging to autoimmune polyglandular syndromes. Some data suggested that AA is more severe if thyroid anomalies are confirmed, including subclinical dysfunction or positive antithyroid antibodies with normal hormone values. However, routine thyroid screening for patients with AA, if the patients are asymptomatic from a thyroid point of view and they have negative personal and family history of autoimmunity, remains controversial. TE, apart from the autoimmune type, associates thyroid anomalies of a hormonal assay (between 5.7% and 17%). FFA, mostly a postmenopausal entity (however, not exclusive), associates a higher prevalence of thyroid conditions (up to 50%) than the general population. However, these might have an age-dependent pattern, thus the association may be incidental since there are a limited number of studies. Overall, alopecia remains a very challenging condition for patients and physicians; a multidisciplinary team is required to improve the outcome and quality of life. The common autoimmune background is suggestive of some types of alopecia and thyroid disorders, yet, the underlying mechanisms are still a matter of debate. AA, TE, FFA, LPP, and, potentially, female pattern hair loss have been found to be connected with thyroid entities, thus a state of awareness from a dual perspective, of trichology and endocrinology, is helpful.

Acanthosis nigricans (AN) has been reported in relation to insulin resistance (IR). We aim to review AN through an endocrine and metabolic perspective focusing on IR in association with metabolic complications such as obesity, diabetes mellitus (DM), and metabolic syndrome (MS) with/without polycystic ovary syndrome (PCOS). We revised English papers on PubMed covering publications from the last 5 years. The current prevalence of AN varies from 4.5 to 74% (or even 100%, depending on the studied population), with equal distribution among females and males. Despite higher incidence with an age-dependent pattern, an alarming escalation of cases has been noted for obesity and MS in younger populations. Most frequent IR-associated sites are the neck, axilla, and knuckles, but unusual locations such as the face have also been reported. Quantitative scales such as Burke have been used to describe the severity of the dermatosis, particularly in correlation with IR elements. Dermoscopic examination are required, for instance, in cases with sulcus cutis, hyperpigmented spots, crista cutis, and papillary projections. A skin biopsy may be necessary, but it is not the rule. Both IR that clinically manifests with or without obesity/MS correlates with AN; most studies are cross-sectional, with only a few longitudinal. The approach varied from screening during school periodic checkups/protocols/programs to subgroups of individuals who were already known to be at high cardio-metabolic risk. AN was associated with type2DM, as well as type 1DM. Females with PCOS may already display metabolic complications in 60–80% of cases, with AN belonging to the associated skin spectrum. AN management depends on underlying conditions, and specific dermatological therapy is not generally required, unless the patient achieves metabolic control, has severe skin lesions, or desires cosmetic improvement. In IR cases, lifestyle interventions can help, including weight control up to bariatric surgery. In addition, metformin is a key player in the field of oral medication against DM type 2, a drug whose indication is extended to PCOS and even to AN itself, outside the specific panel of glucose anomalies. In terms of cosmetic intervention, limited data have been published on melatonin, urea cream, topical retinoids, vitamin D analogs, or alexandrite laser. In conclusion, awareness of IR and its associated clinical features is essential to provide prompt recognition of underlying conditions. AN represents a useful non-invasive surrogate marker of this spectrum in both children and adults. The pivotal role of this dermatosis could massively improve endocrine and metabolic assessments.