This report describes the results of a long term prospective study of 30 women with hyperprolactinemia who were not treated and who underwent yearly clinical, hormonal, and radiographic evaluation for an average of 5.2 yr (range 3-7 yr). At entry into the study 18 women had amenorrhea, 8 had oligomenorrhea, and 4 had regular menstrual periods. The initial mean serum PRL levels did not differ in women grouped according to menstrual function. Nine women (35%) had improvement in clinical symptoms. Serum PRL decreased, and menstrual periods normalized more often in those who initially had oligomenorrhea or regular menstrual periods. In most amenorrheic women serum PRL levels did not decline, and menstrual symptoms did not improve. Six of 30 women had an increase in serum PRL, 14 had no change, and 10 had a decrease, in 6 of whom serum PRL was normal at the last observation. Twenty-seven women had serial radiographic studies. Four (15%) of the 13 women with initially abnormal radiographic findings had normal studies later, 2 had tumor progression, and 7 no change. Four of 14 women who had normal radiographic studies initially developed radiographic evidence of a pituitary tumor, although the radiographic changes were minimal, and no patient developed a macroadenoma or pituitary hypofunction. Increases or decreases in serum PRL did not accurately predict changes in tumor size. Prior estrogen use and previous pregnancies did not increase the likelihood of tumor appearance or enhance tumor growth. The clinical presentation of the patient was an important factor in predicting which patients had a decline in serum PRL and resolution of symptoms. We conclude that patients with hyperprolactinemia are unlikely to have progression of their disease and may, in fact, have clinical and radiographic improvement.

The Natural History of Untreated Hyperprolactinemia: A Prospective Analysis

Both pseudocyesis and delusional pregnancy are said to be rare syndromes, but are reported frequently in developing countries. A distinction has been made between the two syndromes, but the line of demarcation is blurred. The aim of this paper is to review recent cases of pseudocyesis/delusional pregnancy in order to learn more about biopsychosocial antecedents. The recent world literature (2000-2014) on this subject (women only) was reviewed, making no distinction between pseudocyesis and delusional pregnancy. Eighty case histories were found, most of them originating in developing countries. Fifty patients had been given a diagnosis of psychosis, although criteria for making the diagnosis were not always clear. The psychological antecedents included ambivalence about pregnancy, relationship issues, and loss. Very frequently, pseudocyesis/delusional pregnancy occurred when a married couple was infertile and living in a pronatalist society. The infertility was attributed to the woman, which resulted in her experiencing substantial distress and discrimination. When antipsychotic medication was used to treat psychotic symptoms in these women, it led to high prolactin levels and apparent manifestations of pregnancy, such as amenorrhea and galactorrhea, thus reinforcing a false conviction of pregnancy. Developing the erroneous belief that one is pregnant is an understandable process, making the delusion of pregnancy a useful template against which to study the evolution of other, less explicable delusions.

Pseudocyesis, delusional pregnancy, and psychosis: The birth of a delusion.

Despite advances in knowledge about human lactation, clinicians face many problems when advising mothers who are experiencing breastfeeding difficulties that do not respond to normal management strategies. Primary insufficient milk production is now being acknowledged, but incidence rates have not been well studied. Many women have known histories of infertility, polycystic ovary syndrome, obesity, hypertension, insulin resistance, thyroid dysfunction, hyperandrogenism or other hormonal imbalances, while others have no obvious risk factors. Some present with obviously abnormal breasts that are pubescent, tuberous/tubular or asymmetric in shape, raising the question of insufficient mammary gland tissue. Other women have breasts that appear within normal limits yet do not lactate normally. Endocrine disruptors may underlie some of these cases but their impact on human milk production has not been well explored. Similarly, any problem with prolactin such as a deficiency in serum prolactin or receptor number, receptor resistance, or poor bioavailability or bioactivity could underlie some cases of insufficient lactation, yet these possibilities are rarely investigated. A weak or suppressed milk ejection reflex, often assumed to be psychosomatic, could be related to thyroid dysfunction or caused by downstream post-receptor pathway problems. In the absence of sufficient data regarding these situations, desperate mothers may turn to non-evidence-based remedies, sometimes at considerable cost and unknown risk. Research targeted to these clinical dilemmas is critical in order to develop evidence-based strategies and increase breastfeeding duration and success rates.

Unsolved Mysteries of the Human Mammary Gland: Defining and Redefining the Critical Questions from the Lactation Consultant's Perspective

The hypothalamo-pituitary system developed in early vertebrates. Prolactin is an ancient vertebrate hormone released from the pituitary that exerts particularly diverse functions. The purpose of the review is to take a comparative approach in the description of prolactin, its secretion from pituitary lactotrophs, and hormonal functions. Since the reproductive and osmoregulatory roles of prolactin are best established in a variety of species, these functions are the primary subjects of discussion. Different types of prolactin and prolactin receptors developed during vertebrate evolution, which will be described in this review. The signal transduction of prolactin receptors is well conserved among vertebrates enabling us to describe the whole subphylum. Then, the review focuses on the regulation of prolactin release in mammals as we have the most knowledge on this class of vertebrates. Prolactin secretion in response to different reproductive stimuli, such as estrogen-induced release, mating, pregnancy and suckling is detailed. Reproduction in birds is different from that in mammals in several aspects. Prolactin is released during incubation in avian species whose regulation and functional significance are discussed. Little information is available on prolactin in reptiles and amphibians; therefore, they are mentioned only in specific cases to explain certain evolutionary aspects. In turn, the osmoregulatory function of prolactin is well established in fish. The different types of pituitary prolactin in fish play particularly important roles in the adaptation of eutherian species to fresh water environments. To achieve this function, prolactin is released from lactotrophs in hyposmolarity, as they are directly osmosensitive in fish. In turn, the released prolactin acts on branchial epithelia, especially ionocytes of the gill to retain salt and excrete water. This review will highlight the points where comparative data give new ideas or suggest new approaches for investigation in other taxa.

/pdf/secretion-and-function-of-pituitary-prolactin-in-mxotyem25n.pdf

Secretion and Function of Pituitary Prolactin in Evolutionary Perspective

Paired nicking-mediated COL17A1 reframing for junctional epidermolysis bullosa.

© 2013 Lopez et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Physiological and Pathological Hyperprolactinemia: Can We Minimize Errors in the Clinical Practice?

/pdf/physiological-and-pathological-hyperprolactinemia-can-we-imuuk96rea.pdf

Physiological and Pathological Hyperprolactinemia: Can We Minimize Errors in the Clinical Practice?

Importance
Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive disorder caused by pathogenic variants in PLEC1, which encodes plectin. It is characterized by mild mucocutaneous fragility and blistering and muscle weakness. Translational readthrough-inducing drugs, such as repurposed aminoglycoside antibiotics, may represent a valuable therapeutic alternative for untreatable rare diseases caused by nonsense variants.


Objective
To evaluate whether systemic gentamicin, at a dose of 7.5 mg/kg/d for 14 consecutive days, is clinically beneficial in a patient with EBS-MD.


Design, Setting, and Participants
A single patient in Madrid, Spain, received 2 treatment courses with gentamicin on July 2019 and February 2020 with a follow-up period of 120 and 150 days, respectively.


Results
In this case report of a woman in her 30s with EBS-MD, before gentamicin treatment, the patient had mucocutaneous involvement, skeletal and respiratory muscle weakness, and myalgia that negatively affected her quality of life. Outcomes were evaluated with extensive laboratory tests and clinical scales. No nephrotoxic or ototoxic effects were detected after intravenous gentamicin administration. Gentamicin treatment was followed by plectin expression in the skin for at least 5 months. Although minimal changes were noted in skeletal muscle function (as measured by the Hammersmith functional motor scale and its expanded version: 6/40 to 7/40 and from 10/66 to 11/66, respectively) and respiratory musculature (maximal inspiratory and expiratory pressures D0 vs D16, MIP: 2.86 vs 3.63 KPa and MEP: 2.93 vs 4.63 KPa), myalgia disappeared (VAS dropped from 6 to 0), and quality of life improved (EuroQoL-5D-3L pain and anxiety dropped from 2 to 1).


Conclusions and Relevance
The findings of this single case report suggest that gentamicin treatment may help suppress PLEC1 premature termination codons and induce plectin expression in EBS-MD primary keratinocytes and skin. Our study suggests that gentamicin may play an important role in treating EBS-MD owing to nonsense variants.

Evaluation of Systemic Gentamicin as Translational Readthrough Therapy for a Patient With Epidermolysis Bullosa Simplex With Muscular Dystrophy Owing to PLEC1 Pathogenic Nonsense Variants.

Recessive dystrophic epidermolysis bullosa, a devastating skin fragility disease characterized by recurrent skin blistering, scarring, and a high risk of developing squamous cell carcinoma is caused by mutations in COL7A1, the gene encoding type VII collagen, which is the major component of the anchoring fibrils that bind the dermis and epidermis. Ex vivo correction of COL7A1 by gene editing in patients' cells has been achieved before. However, in vivo editing approaches are necessary to address the direct treatment of the blistering lesions characteristic of this disease. We have now generated adenoviral vectors for CRISPR-Cas9 delivery to remove exon 80 of COL7A1, which contains a highly prevalent frameshift mutation in Spanish patients. For in vivo testing, a humanized skin mouse model was used. Efficient viral transduction of skin was observed after excisional wounds generated with a surgical punch on regenerated patient skin grafts were filled with the adenoviral vectors embedded in a fibrin gel. Type VII collagen deposition in the basement membrane zone of the wounded areas treated with the vectors correlated with restoration of dermal-epidermal adhesion, demonstrating that recessive dystrophic epidermolysis bullosa (RDEB) patient skin lesions can be directly treated by CRISPR-Cas9 delivery in vivo. 

https://doi.org/10.1016/j.omtm.2022.09.005

Marta Robles García

Papers

Physiological and Pathological Hyperprolactinemia: Can We Minimize Errors in the Clinical Practice?

Paired nicking-mediated COL17A1 reframing for junctional epidermolysis bullosa.

Evaluation of Systemic Gentamicin as Translational Readthrough Therapy for a Patient With Epidermolysis Bullosa Simplex With Muscular Dystrophy Owing to PLEC1 Pathogenic Nonsense Variants.

Preclinical model for phenotypic correction of dystrophic epidermolysis bullosa by in vivo CRISPR-Cas9 delivery using adenoviral vectors