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Macroprolactinemia as a diagnostic pitfall in hyperprolactinemia: a systematic review and quantitative synthesis.

CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as studies vary in confirmation method, assay platform, polyethylene glycol (PEG) recovery cutoff, and reporting of prolactin measurement. EVIDENCE ACQUISITION: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar were systematically searched. Eligible studies reported macroprolactinemia-specific quantitative prolactin data in patients with confirmed macroprolactinemia defined by PEG precipitation, gel filtration chromatography (GFC), or both. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were summarized using study-level descriptive synthesis. The review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020 guidelines. EVIDENCE SYNTHESIS: Forty-five studies encompassing 2853 macroprolactinemia cases from 21 413 screened patients with hyperprolactinemia across 22 countries were included. Among 33 studies eligible for primary quantitative analysis, the median study-level central total prolactin attributed to macroprolactinemia was 61.4 ng/mL ([IQR] 42.0-80.0; range 28.1-137.6), and the median study-level post-PEG monomeric prolactin was 11.7 ng/mL (IQR 8.3-13.2; range 4.0-17.0)). The median study-level maximum total prolactin was 264.5 ng/mL (IQR 97.0-425.5; range 81.8-663.0); extreme elevations were attributable to coexisting prolactinomas. CONCLUSION: In confirmed macroprolactinemia, total prolactin elevation is typically moderate, and post-PEG monomeric prolactin is usually within or near the normal range. The post-PEG monomeric prolactin value, rather than percent recovery alone, is the most informative parameter for distinguishing isolated macroprolactinemia from coexisting true hyperprolactinemia. These quantitative benchmarks may help clinicians to avoid unnecessary investigation or treatment.

Humans

Source of diagnostic pitfalls in renal sonography.

In the evaluation of 116 renal masses 91 (80%) were interpreted as cystic and 25 (20%) as solid. Additional evaluation by arteriography and finally surgery showed that 3 of the 25 initially believed to be solid proved to be cystic. These three renal masses with internal echoes on ultrasound were found at surgery to be either collections of contiguous cysts or loculated cysts with calcification. These conditions are believed to represent a source of diagnostic pitfalls in renal sonography.

Adult

CT during arterial portography: diagnostic pitfalls.

Computed tomography (CT) during arterial portography (CTAP) is an important technique for evaluating the liver before hepatic tumor resection. With this technique, most tumors are of low attenuation compared with that of enhancing parenchyma. At times, low-attenuation lesions are encountered that represent perfusion abnormalities rather than tumor deposits. These perfusion abnormalities can be categorized as (a) those resulting from improper technique; (b) those extending from hilum to capsule (straight-line sign), with or without an obstructing mass; (c) perihilar and periligamentous abnormalities; (d) subcapsular defects (linear or wedge shaped); and (e) those seen with cirrhosis or regenerating nodules. Adjuvant use of delayed CT, magnetic resonance imaging, and intraoperative ultrasound aids in characterization of these nontumorous defects, thereby improving specificity. The authors conclude that when potential candidates are evaluated for hepatic tumor resection, knowledge of the existence of the various diagnostic pitfalls of CTAP and their imaging characteristics is imperative to avoid inadvertent false results.

Angiography, Digital Subtraction

Vertebral osteomyelitis. Still a diagnostic pitfall.

Vertebral osteomyelitis is still a diagnostic problem. Nonspecific symptoms (low-grade fever, malaise, and weight loss) may dominate. Specific infections may be suggested by the history, and the diagnosis may be reinforced by a transient response to antibiotics. The patient may have symptoms resulting from a secondary paravertebral abscess. Even with fever, back pain, and point tenderness over the vertebral column, the correct diagnosis may not be considered. Predisposing conditions include drug addiction, instrumentation of the infected urinary tract, bacteremia from other causes, or previous back surgery. Diagnosis is made by roentgenographic studies and isolation of the causative organism from blood cultures or from the infected area. Staphylococcus aureus is the most common pathogen, although other microorganisms may be responsible. Intensive intravenous antibiotic treatment appears to be curative, without surgical debridement, external stabilization, or porlonged oral administration of antibiotics.

Adult

Respiratory-onset peripartum cardiomyopathy: a systematic review of diagnostic pitfalls and clinical outcomes.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) may initially present with prominent respiratory symptoms that resemble primary pulmonary disease, particularly in late pregnancy and the early postpartum period. In clinical practice, this presentation often triggers alternative diagnostic pathways, introducing delay at a time when rapid cardiac assessment is critical. Although respiratory-dominant presentations are repeatedly described across case-based and observational reports, they have not been systematically examined as a distinct diagnostic pathway within the PPCM literature. CONTENT: This PRISMA-guided systematic review synthesized evidence relating to respiratory-onset presentations of PPCM. Major databases and registers were searched comprehensively. Following screening of 589 records and full-text assessment of 145 reports, 49 studies met inclusion criteria. Twenty studies were qualitatively prioritized for narrative synthesis using ROBIS-informed methodological appraisal. Evidence was examined across diagnostic misclassification patterns, cardiopulmonary mechanisms, differential diagnoses, investigative strategies, and acute and longitudinal management considerations. SUMMARY: Respiratory-led presentations were commonly misattributed to asthma, pneumonia, pulmonary embolism, or perioperative causes, with diagnostic delay frequently reported. Across heterogeneous study designs, cardiogenic pulmonary edema with left-ventricular systolic dysfunction emerged as a recurring unifying mechanism. Early use of echocardiography, natriuretic peptides, and targeted imaging consistently aided differentiation from primary respiratory pathology. Severe clinical deterioration was often described in the context of delayed recognition. OUTLOOK: Respiratory-onset PPCM represents a high-risk diagnostic pathway rather than a discrete disease entity. Prospective registries, standardized diagnostic algorithms, and closer integration of obstetric and cardiopulmonary care are needed to refine early recognition and improve maternal outcomes.

Humans

Obstructive nephropathy with infection. A diagnostic pitfall.

Four patients with indistinct abdominal symptoms associated with fever are presented. In all cases the diagnosis proved to be obstructive nephropathy with infection. The proper treatment of the patients was delayed, essentially because of a non-investigative diagnostic attitude. The necessity of making a correct diagnosis in the early course of an acute abdominal disease with fever is emphasised and some investigations that may be of great value for reaching a precise diagnosis are indicated.

Aged

[XX-male-syndrome. Pathogenesis and aspects of diagnostic pitfalls (author's transl)].

A boy with XX-karyotype displayed classical features of Klinefelter's syndrome. In the nuclei of hair root cells Barr-bodies were present as well as brightly fluorescent (F-)bodies resembling closely a Y-body. In lymphocyte metaphases, however, this F-body of the interphase nuclei corresponded to a brightly fluorescent segment of the short arm of a D15-chromosome was found in the father's karyotype. This case does not give convincing support to any of the theories suggested in the etiology of the XX-male phenomenon.

Adolescent

Multiple renal masses in patients with renal cell carcinoma: diagnostic pitfalls and surgical implications.

Additional renal masses were found in the same or contralateral kidney in 41 of 131 patients with renal cell carcinoma. In 35 of the patients the additional renal masses were simple renal cysts situated in the kidney contralateral to the renal cell carcinoma in 16 patients, in the same kidney in 11 and bilaterally in 8 patients. Four patients had bilateral renal cell carcinomas. One patient had polycystic kidney disease as well as renal cell carcinoma and another patient had a benign tumour in the contralateral kidney. In 3 of the 30 patients with additional renal masses in the kidney contralateral to the renal cell carcinoma the radiologic examinations were insufficient to exclude malignancy. Only explorative surgery could establish a true diagnosis of these masses.

Adult

Spinal cord injury in children and adolescents: diagnostic pitfalls and therapeutic considerations in the acute stage [proceedings].

Traumatic spinal cord lesions in children are infrequent (2 to 5 per cent of all cases admitted to specialised paraplegic centres depending on whether the upper age limit is set at 10 or 15 years). Traffic accidents are responsible for at least 50 per cent of the lesions; playground accidents and various sports add another 35 per cent. A large proportion of the accidents have been found to be related to the child's normal desire for adventure and exploration. The segment most frequently involved in our own series of 18 cases was the cervical and upper thoracic spine. Histopathological studies have shown that splitting of the cartilaginous end-plate in the growth zone of the vertebrae is a common finding. Radiological signs of spinal trauma are less evident than in adults; they may be totally missing. Precise neurological assessment must rely on repeated examination and close clinical observation, especially in the comatous child with a head injury. Spinal cord involvement must be suspected and the child treated as a paraplegic until definite proof of a normal neurological status is available. Due to a highly labile water electrolyte balance in the early post-traumatic stage and considerable fluctuations in plasma volume and temperature regulation, permanent monitoring of the cardiovascular function, body temperature and diuresis is mandatory. In children below the age of 10, deep vein thrombosis and embolism are exceptional (sepsis creates a high-risk situation requiring anticoagulation). In the initial treatment of spinal injury only conservative measures should be considered; there are no indications for laminectomy, nor for spinal fusion. In the tetraplegic child below the age of 6, skull-traction should be avoided and immobilisation of the cervical segment achieved by bilateral padded head-rests.

Acute Disease

The diagnostic pitfalls of subarachnoid hemorrhage from intracranial aneurysms.

The subtle manner in which subarachnoid hemorrhage frequently presents may delay appropriate treatment. The patient may deteriorate and die from aneurysmal rebleeding or from cerebral ischemia associated with vasospasm before the true nature of the disease is recognized. Five patients are described in whom subarachnoid hemorrhage was initially not recognized. Pitfalls in diagnosis are discussed, and an outline is presented for the evaluation of patients suspected of harboring ruptured intracranial aneurysms.

Adult