Researcher Shaimaa Diaa Khudr Jassim has completed her thesis entitled “The Role of 11β-Hydroxysteroid Dehydrogenase Type 1, Collagen IV, Glial Fibrillary Acidic Protein, and Neopterin in Iraqi Patients with Cushing’s Disease before and after Treatment,” under the supervision of Prof. Dr. Rasha Zuhair Jassim. The thesis was evaluated by a committee comprising Prof. Dr. Taghreed Uloom Mohammed, Chair; Prof. Dr. Hind Shakir Ahmed, Member; Prof. Dr. Warkaa Tuma Saloom, Member; Prof. Dr. Norhan Khalid Shafeeq, Member; and Asst. Prof. Dr. Abdul Qader Mohammed Abdul Qader, Member.
The thesis addresses Cushing’s disease, an important endocrine disorder associated with excessive exposure to cortisol and a wide range of metabolic, hormonal, neurological, and immune-related effects. The significance of the study lies in its investigation of a panel of biochemical biomarkers that may contribute to a better understanding of the underlying pathophysiological mechanisms of the disease and the biochemical changes associated with Cushing’s disease before and after treatment.
The study aimed to investigate the relationship between a set of predictive biomarkers—including 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), Collagen IV, glial fibrillary acidic protein (GFAP), and neopterin—and the pathophysiological mechanisms of Cushing’s disease among Iraqi male and female patients.
The research also sought to elucidate the relationships involving cortisol, adrenocorticotropic hormone (ACTH), and growth hormone (GH), together with the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), selected serum electrolytes including sodium, potassium, calcium, and chloride, as well as body mass index (BMI) among Iraqi patients with Cushing’s disease.
Another major aspect of the thesis was to investigate the biological effects of glucocorticoid derivatives, particularly prednisolone and hydrocortisone, on predictive and diagnostic biomarkers in patients with Cushing’s disease. Comparing biomarker profiles before and after treatment provides an important basis for understanding biological changes associated with therapeutic intervention.
The study further examined whether sex influences predictive and diagnostic biomarkers, thereby contributing to a better understanding of potential biological differences between male and female patients and supporting the development of more precise approaches to investigating biomarkers associated with endocrine disorders.
Based on the study findings, the researcher proposed several recommendations for future research. These included conducting further investigations into the effects of different corticosteroid medications, including their types, doses, and treatment durations, on the same biochemical biomarkers, thereby expanding the understanding of treatment-associated biochemical alterations.
The researcher also recommended conducting similar studies among younger age groups to investigate the early onset of Cushing’s disease and examine the effects of hypercortisolism on growth and development. In addition, the study recommended further investigation of biochemical markers associated with the psychological and mental status of patients with Cushing’s disease, including serotonin and melatonin, in order to provide a more comprehensive understanding of the systemic effects of the disorder.
The study directly contributes to United Nations Sustainable Development Goal 3 (SDG 3): Good Health and Well-Being by advancing scientific knowledge of Cushing’s disease and investigating biomarkers associated with the disease and its response to treatment. Such research may support future efforts in disease assessment, monitoring, and clinical evaluation.
The study also relates to Sustainable Development Goal 5 (SDG 5): Gender Equality, particularly through its investigation of the potential influence of sex on predictive and diagnostic biomarkers. This aspect highlights the importance of considering biological differences between males and females in biomedical and biochemical research.
Overall, the research reflects an evidence-based scientific approach to understanding complex endocrine disorders through the integrated investigation of biomarkers, hormonal profiles, and biochemical parameters. It contributes to the advancement of biomedical and biochemical research aimed at improving healthcare knowledge and supporting better understanding of endocrine diseases within the Iraqi population.
Cushing’s disease (CD) is a specific type of Cushing’s syndrome (CS) characterized by over production of cortisol from the adrenal cortex induced by ACTH secreted by pituitary neuro-endocrine adenoma. This condition causes a lot of comorbidities which are partially understood, so the aim of the present study is to innovate a biochemical relationship between predictive biochemical markers (11-βHSD1, collagen IV, GFAP and neopterin) and the etiology of CD in Iraqi patients (males and females) and to submit a resonable clarification for the exact role of the definite biochemical parameters: (cortisol, ACTH, GH, FSH, LH, sodium, potassium, calcium, chloride and BMI) in the same patients. Also, the present study aims to examine and highlight the biochemical action of the synthetic glucocorticoids (prednisolone and hydrocortisone) as a treatment on both the predictive and definite parameter and to recognize if those parameters are influenced by the gender. The medical and laboratory parts of the present study were conducted from November 2023 to the end of June 2024. Blood sampling was performed in Baghdad Teaching Hospital (The medical City) and Al-Yarmook Teaching Hospital while the biochemical determinations were conducted in the International Center for Research and Development /Baghdad. The study protocol involved six groups distributed according to the gender (males and females) and the pharmaceutical status (untreated and treated cases) Remarkably, the patients groups were compared with healthy subjects as control groups: G₁ composed of (25) healthy males and G2 composed of (25) healthy females in the same age range as the patients groups. G3 composed of (25) newly diagnosed (untreated) males with CD, G4 composed of (25) newly diagnosed (untreated) females with CD, G5 composed of (25) CD males treated with prednisolone and hydrocortisone and G6 composed of (25) CD females treated with prednisolone. The levels of the predictive markers (11β-HSD1, Collagen IV, GFAP and neopterin) and the definite parameters (cortisol, ACTH, GH, FSH, LH, sodium, potassium, calcium, chloride and BMI) were determined in sera of all patients and control groups, subsequently the data were statistically analysed according to student t-test (to compare between two groups) and ANOVA one way (to compare among three groups). The results have reported that 11β-HSD1 , collagen IV, GFAP and neopterin are novel biochemical markers for CD patients with highly significant increase in both males and females regarding 11β-HSD1 , GFAP and neopterin and highly significant decrease regarding Collagen IV by highlighting the hypercortsolism and the disordered HPA axis, the immune system (in particular the macrophages) and the central nervous system (in particular the astrocytes). Also, the present study has submitted a detailed clarification regarding the higher levels of cortisol as a diagnositic parameter and confirmed that all the selected CS patients are CD cases on the basis of higher levels of ACTH. Moreover, the present study has supported other previous and recent studies regarding the lower levels of GH and submitted a comprehensive clarification for the lower levels of FSH and LH in the same patients by highlighting the neuro protective effects of these hormones and indicated that hyponatremia, hypokalemia, hypocalcemia and minimal hyper-chloremia are obivious features for the same patients. Remarkably, the present study has revealed that BMI was non significantly increased in CD patients. On the other hand, the present study is the first suggesting, a resonable clarification for the inhibitory effect of the synthetic glucocorticoids (prednisolone and hydrocortisone) on HPA axis which suppress the higher levels of cortisol, ACTH and 11β-HSD1 for CD patients by highlighting the similarity between the synthetic and natural glucocorticoids which promote GR complexes and negatively inhibit HPA axis (with a great inhibitory effect on ACTH in females). In the same context, the present study has submitted novel outcomes regarding the impact of prednisolone and hydrocortisone on the levels of Collagen IV, GFAP, neopterin, GH, FSH and LH in the same patients whereby the effect was minimal on collagen IV, FSH, LH and pivotal in trying to shift GFAP neopterin and GH into the balance on the basis of the anti-inflammatory protective effect on the synthetic glucocorticoids. Unexpectly, the BMI was increased in the treated CD patients compared with the untreated newly diagnosed patients revealing an adverse effect of the synthetic glucocorticoids (prednisolone and hydrocortisone) on the BMI while the same glucocorticoids have exhibited a good action on blood electrolytes (sodium, potassium, calcium and chloride) compared with both the treated and control subjects (except potassium in females whose balance was affected by a prednisolone adverse effect ). Finally, the present study has revealed that the levels of ACTH, 11β-HSD1, collagen IV, GFAP, neopterin, GH, LH, chloride and the values of BMI were not affected by the gender while the levels of cortisol, FSH, sodium, potassium and calcium have statistically contrasting values when each one was compared between the two genders.
